LYNPARZA- olaparib tablet, film coated AstraZeneca Pharmaceuticals LP----------

HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use LYNPARZA safely andeffectively. See full prescribing information for LYNPARZA.

LYNPARZA (olaparib) tablets, for oral useInitial U.S. Approval: 2014

RECENT MAJOR CHANGESIndications and Usage (1) 05/2020Dosage and Administration (2) 12/2020Warnings and Precautions, Myelodysplastic Syndrome/Acute Myeloid Leukemia (5.1) 03/2021Warnings and Precautions, Venous Thromboembolic Events (5.4) 05/2020

INDICATIONS AND USAGELynparza is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:Ovarian cancer

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Breast cancer

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Pancreatic cancer

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Prostate cancer

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for the maintenance treatment of adult patients with deleterious or suspected deleterious germline orsomatic BRCA-mutated advanced epithelial ovarian, fallopian tube or primary peritoneal cancer whoare in complete or partial response to first-line platinum-based chemotherapy. Select patients fortherapy based on an FDA-approved companion diagnostic for Lynparza. (1.1, 2.1)in combination with bevacizumab for the maintenance treatment of adult patients with advancedepithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial responseto first-line platinum-based chemotherapy and whose cancer is associated with homologousrecombination deficiency (HRD)-positive status defined by either:

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a deleterious or suspected deleterious BRCA mutation, and/orgenomic instability.

Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza (1.2, 2.1).for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube orprimary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy.(1.3)for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated(gBRCAm) advanced ovarian cancer who have been treated with three or more prior lines ofchemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic forLynparza. (1.4, 2.1)

for the treatment of adult patients with deleterious or suspected deleterious gBRCAm, HER2-negativemetastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant ormetastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have beentreated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Selectpatients for therapy based on an FDA-approved companion diagnostic for Lynparza. (1.5, 2.1)

for the maintenance treatment of adult patients with deleterious or suspected deleterious gBRCAmmetastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of afirst-line platinum-based chemotherapy regimen. Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza. (1.6, 2.1)

for the treatment of adult patients with deleterious or suspected deleterious germline or somatichomologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostatecancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone.Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza. (1.7, 2.1)

DOSAGE AND ADMINISTRATION

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DOSAGE FORMS AND STRENGTHSTablets: 150 mg, 100 mg (3)

CONTRAINDICATIONSNone. (4)

WARNINGS AND PRECAUTIONS

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ADVERSE REACTIONSMost common adverse reactions (≥10%) in clinical trials:

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To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDAat 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

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USE IN SPECIFIC POPULATIONSLactation: Advise women not to breastfeed. (8.2) See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.

Revised: 6/2021

FULL PRESCRIBING INFORMATION: CONTENTS*1 INDICATIONS AND USAGE

1.1 First-Line Maintenance Treatment of BRCA-mutated Advanced Ovarian Cancer1.2 First-line Maintenance Treatment of HRD-positive Advanced Ovarian Cancer inCombination with Bevacizumab1.3 Maintenance Treatment of Recurrent Ovarian Cancer

Recommended dosage is 300 mg taken orally twice daily with or without food. See Full PrescribingInformation for the recommended duration. (2.2)Patients receiving Lynparza for mCRPC should also receive a gonadotropin-releasing hormone (GnRH)analog concurrently or should have had bilateral orchiectomy. (2.2)For moderate renal impairment (CLcr 31-50 mL/min), reduce Lynparza dosage to 200 mg orally twicedaily. (2.5)

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in approximately 1.5% ofpatients exposed to Lynparza monotherapy and the majority of events had a fatal outcome. Monitorpatients for hematological toxicity at baseline and monthly thereafter. Discontinue if MDS/AML isconfirmed. (5.1)Pneumonitis: Occurred in 0.8% of patients exposed to Lynparza, and some cases were fatal. Interrupttreatment if pneumonitis is suspected. Discontinue if pneumonitis is confirmed. (5.2)Embryo-Fetal Toxicity: Can cause fetal harm. Advise of the potential risk to a fetus and to useeffective contraception. (5.3, 8.1, 8.3)Venous thromboembolic events including pulmonary embolism occurred in 7% of patients withmCRPC. Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolismand treat as medically appropriate. (5.4)

as a single agent were nausea, fatigue (including asthenia), anemia, vomiting, diarrhea, decreasedappetite, headache, dysgeusia, cough, neutropenia, dyspnea, dizziness, dyspepsia, leukopenia, andthrombocytopenia. (6.1)in combination with bevacizumab were nausea, fatigue (including asthenia), anemia, lymphopenia,vomiting, diarrhea, neutropenia, leukopenia, urinary tract infection, and headache. (6.1)

Strong or moderate CYP3A inhibitors: Avoid concomitant use. If concomitant use cannot be avoided,reduce Lynparza dosage. (2.4, 7.2, 12.3)Strong or moderate CYP3A inducers: Avoid concomitant use. (7.2, 12.3)

1.4 Advanced Germline BRCA-mutated Ovarian Cancer After 3 or More Lines ofChemotherapy1.5 Germline BRCA-mutated HER2-negative Metastatic Breast Cancer1.6 First-Line Maintenance Treatment of Germline BRCA-mutated MetastaticPancreatic Adenocarcinoma1.7 HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer

2 DOSAGE AND ADMINISTRATION2.1 Patient Selection2.2 Recommended Dosage2.3 Dosage Modifications for Adverse Reactions2.4 Dosage Modifications for Concomitant Use with Strong or Moderate CYP3AInhibitors2.5 Dosage Modifications for Renal Impairment

3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND PRECAUTIONS

5.1 Myelodysplastic Syndrome/Acute Myeloid Leukemia5.2 Pneumonitis5.3 Embryo-Fetal Toxicity5.4 Venous Thromboembolic Events

6 ADVERSE REACTIONS6.1 Clinical Trial Experience6.2 Postmarketing Experience

7 DRUG INTERACTIONS7.1 Use with Anticancer Agents7.2 Effect of Other Drugs on Lynparza

8 USE IN SPECIFIC POPULATIONS8.1 Pregnancy8.2 Lactation8.3 Females and Males of Reproductive Potential8.4 Pediatric Use8.5 Geriatric Use8.6 Renal Impairment8.7 Hepatic Impairment

11 DESCRIPTION12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action12.2 Pharmacodynamics12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES14.1 First-Line Maintenance Treatment of BRCA-mutated Advanced Ovarian Cancer14.2 First-line Maintenance Treatment of HRD-positive Advanced Ovarian Cancer inCombination with Bevacizumab14.3 Maintenance Treatment of Recurrent Ovarian Cancer14.4 Advanced Germline BRCA-mutated Ovarian Cancer Treated with 3 or More PriorLines of Chemotherapy14.5 Treatment of Germline BRCA-mutated HER2-negative Metastatic Breast Cancer14.6 First-Line Maintenance Treatment of Germline BRCA-mutated Metastatic

Pancreatic Adenocarcinoma14.7 HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer

16 HOW SUPPLIED/STORAGE AND HANDLING17 PATIENT COUNSELING INFORMATION*

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

1.1 First-Line Maintenance Treatment of BRCA-mutated Advanced OvarianCancerLynparza is indicated for the maintenance treatment of adult patients with deleterious orsuspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian,fallopian tube or primary peritoneal cancer who are in complete or partial response tofirst-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza [see Dosage and Administration (2.1)].

1.2 First-line Maintenance Treatment of HRD-positive Advanced OvarianCancer in Combination with BevacizumabLynparza is indicated in combination with bevacizumab for the maintenance treatment ofadult patients with advanced epithelial ovarian, fallopian tube or primary peritonealcancer who are in complete or partial response to first-line platinum-basedchemotherapy and whose cancer is associated with homologous recombinationdeficiency (HRD)-positive status defined by either:

Select patients for therapy based on an FDA-approved companion diagnostic forLynparza [see Dosage and Administration (2.1)].

1.3 Maintenance Treatment of Recurrent Ovarian CancerLynparza is indicated for the maintenance treatment of adult patients with recurrentepithelial ovarian, fallopian tube or primary peritoneal cancer, who are in complete orpartial response to platinum-based chemotherapy.

1.4 Advanced Germline BRCA-mutated Ovarian Cancer After 3 or More Linesof ChemotherapyLynparza is indicated for the treatment of adult patients with deleterious or suspecteddeleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have beentreated with three or more prior lines of chemotherapy. Select patients for therapybased on an FDA-approved companion diagnostic for Lynparza [see Dosage and

Sections or subsections omitted from the full prescribing information are not listed.

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a deleterious or suspected deleterious BRCA mutation, and/orgenomic instability.

Administration (2.1)].

1.5 Germline BRCA-mutated HER2-negative Metastatic Breast CancerLynparza is indicated for the treatment of adult patients with deleterious or suspecteddeleterious gBRCAm, HER2-negative metastatic breast cancer, who have been treatedwith chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients withhormone receptor (HR)-positive breast cancer should have been treated with a priorendocrine therapy or be considered inappropriate for endocrine therapy. Select patientsfor therapy based on an FDA-approved companion diagnostic for Lynparza [see Dosageand Administration (2.1)].

1.6 First-Line Maintenance Treatment of Germline BRCA-mutated MetastaticPancreatic AdenocarcinomaLynparza is indicated for the maintenance treatment of adult patients with deleterious orsuspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose diseasehas not progressed on at least 16 weeks of a first-line platinum-based chemotherapyregimen. Select patients for therapy based on an FDA-approved companion diagnosticfor Lynparza [see Dosage and Administration (2.1)].

1.7 HRR Gene-mutated Metastatic Castration-Resistant Prostate CancerLynparza is indicated for the treatment of adult patients with deleterious or suspecteddeleterious germline or somatic homologous recombination repair (HRR) gene-mutatedmetastatic castration-resistant prostate cancer (mCRPC) who have progressed followingprior treatment with enzalutamide or abiraterone. Select patients for therapy based onan FDA-approved companion diagnostic for Lynparza [see Dosage and Administration(2.1)].

2 DOSAGE AND ADMINISTRATION

2.1 Patient SelectionInformation on FDA-approved tests for the detection of genetic mutations is available athttp://www.fda.gov/companiondiagnostics.Select patients for treatment with Lynparza based on the presence of deleterious orsuspected deleterious HRR gene mutations, including BRCA mutations, or genomicinstability based on the indication, biomarker, and sample type (Table 1).

Table 1 Biomarker Testing for Patient SelectionIndication Biomarker Sample type

Tumor Blood Plasma(ctDNA)

First-line maintenance treatment ofgermline or somatic BRCAmadvanced ovarian cancer

BRCA1m, BRCA2m X X

First-line maintenance treatment ofHRD-positive advanced ovarian BRCA1m, BRCA2m X

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cancer in combination withbevacizumab

and/or genomic instability X

Maintenance treatment ofrecurrent ovarian cancer

No requirement forbiomarker testing

Advanced gBRCAm ovarian cancer gBRCA1m, gBRCA2m XgBRCAm HER2-negative metastaticbreast cancer gBRCA1m, gBRCA2m XFirst-line maintenance treatment ofgermline BRCA-mutated metastaticpancreatic adenocarcinoma

gBRCA1m, gBRCA2m X

Germline or somatic HRR gene-mutated metastatic castration-resistant prostate cancer

ATMm, BRCA1m,BRCA2m, BARD1m,BRIP1m, CDK12m,CHEK1m, CHEK2m,FANCLm, PALB2m,

RAD51Bm, RAD51Cm,RAD51Dm, RAD54Lm

X

gBRCA1m, gBRCA2m XATMm, BRCA1m,

BRCA2mX

2.2 Recommended DosageThe recommended dosage of Lynparza is 300 mg taken orally twice daily, with orwithout food.If a patient misses a dose of Lynparza, instruct patient to take their next dose at itsscheduled time.Instruct patients to swallow tablets whole. Do not chew, crush, dissolve, or divide tablet.First-Line Maintenance Treatment of BRCA-mutated Advanced Ovarian CancerContinue treatment until disease progression, unacceptable toxicity, or completion of 2years of treatment. Patients with a complete response (no radiological evidence ofdisease) at 2 years should stop treatment. Patients with evidence of disease at 2 years,who in the opinion of the treating healthcare provider can derive further benefit fromcontinuous treatment, can be treated beyond 2 years.First-Line Maintenance Treatment of HRD-positive Advanced Ovarian Cancer inCombination with BevacizumabContinue Lynparza treatment until disease progression, unacceptable toxicity, orcompletion of 2 years of treatment. Patients with a complete response (no radiologicalevidence of disease) at 2 years should stop treatment. Patients with evidence of diseaseat 2 years, who in the opinion of the treating healthcare provider can derive furtherbenefit from continuous Lynparza treatment, can be treated beyond 2 years.When used with Lynparza, the recommended dose of bevacizumab is 15 mg/kg everythree weeks. Bevacizumab should be given for a total of 15 months including the periodgiven with chemotherapy and given as maintenance. Refer to the Prescribing

Where testing fails or tissue sample is unavailable/insufficient, or when germline testing isnegative, consider using an alternative test, if available.

Information for bevacizumab when used in combination with Lynparza for moreinformation.Recurrent Ovarian Cancer, Germline BRCAm Advanced Ovarian Cancer, HER2-negativeMetastatic Breast Cancer, Metastatic Pancreatic Adenocarcinoma, and HRR Gene-mutated Metastatic Castration-Resistant Prostate CancerContinue treatment until disease progression or unacceptable toxicity for:

Patients receiving Lynparza for mCRPC should also receive a gonadotropin-releasinghormone (GnRH) analog concurrently or should have had bilateral orchiectomy.

2.3 Dosage Modifications for Adverse ReactionsTo manage adverse reactions, consider interruption of treatment or dose reduction. Therecommended dose reduction is 250 mg taken twice daily.If a further dose reduction is required, then reduce to 200 mg taken twice daily.

2.4 Dosage Modifications for Concomitant Use with Strong or ModerateCYP3A InhibitorsAvoid concomitant use of strong or moderate CYP3A inhibitors with Lynparza.If concomitant use cannot be avoided, reduce Lynparza dosage to:

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After the inhibitor has been discontinued for 3 to 5 elimination half-lives, resume theLynparza dose taken prior to initiating the CYP3A inhibitor [see Drug Interactions (7.2)and Clinical Pharmacology (12.3)].

2.5 Dosage Modifications for Renal ImpairmentModerate Renal ImpairmentIn patients with moderate renal impairment (CLcr 31-50 mL/min), reduce the Lynparzadosage to 200 mg orally twice daily [see Use in Specific Populations (8.6) and ClinicalPharmacology (12.3)].

3 DOSAGE FORMS AND STRENGTHSTablets:

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Maintenance treatment of recurrent ovarian cancerAdvanced germline BRCA-mutated ovarian cancerGermline BRCA-mutated HER-2 negative metastatic breast cancerFirst-line maintenance treatment of germline BRCA-mutated metastaticpancreatic adenocarcinoma.HRR gene-mutated metastatic castration-resistant prostate cancer

100 mg twice daily when used concomitantly with a strong CYP3A inhibitor.150 mg twice daily when used concomitantly with a moderate CYP3A inhibitor.

150 mg: green to green/grey, oval, bi-convex, film-coated, with debossment

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4 CONTRAINDICATIONSNone.

5 WARNINGS AND PRECAUTIONS

5.1 Myelodysplastic Syndrome/Acute Myeloid LeukemiaMyelodysplastic syndrome (MDS)/Acute Myeloid Leukemia (AML) has occurred in patientstreated with Lynparza and some cases were fatal.In clinical studies enrolling 2901 patients with various cancers who received Lynparza asa single agent [see Adverse Reactions (6.1)], the cumulative incidence of MDS/AML wasapproximately 1.5% (43/2901). Of these, 51% (22/43) had a fatal outcome. The medianduration of therapy with Lynparza in patients who developed MDS/AML was 2 years(range: < 6 months to > 10 years). All of these patients had received previouschemotherapy with platinum agents and/or other DNA damaging agents includingradiotherapy.Do not start Lynparza until patients have recovered from hematological toxicity causedby previous chemotherapy (≤ Grade 1). Monitor complete blood count for cytopenia atbaseline and monthly thereafter for clinically significant changes during treatment. Forprolonged hematological toxicities, interrupt Lynparza and monitor blood counts weeklyuntil recovery. If the levels have not recovered to Grade 1 or less after 4 weeks, referthe patient to a hematologist for further investigations, including bone marrow analysisand blood sample for cytogenetics. If MDS/AML is confirmed, discontinue Lynparza.

5.2 PneumonitisIn clinical studies enrolling 2901 patients with various cancers who received Lynparza asa single agent [see Adverse Reactions (6.1)], the incidence of pneumonitis, including fatalcases, was 0.8% (24/2901). If patients present with new or worsening respiratorysymptoms such as dyspnea, cough and fever, or a radiological abnormality occurs,interrupt Lynparza treatment and promptly assess the source of the symptoms. Ifpneumonitis is confirmed, discontinue Lynparza treatment and treat the patientappropriately.

5.3 Embryo-Fetal ToxicityLynparza can cause fetal harm when administered to a pregnant woman based on itsmechanism of action and findings in animals. In an animal reproduction study,administration of olaparib to pregnant rats during the period of organogenesis causedteratogenicity and embryo-fetal toxicity at exposures below those in patients receivingthe recommended human dose of 300 mg twice daily. Apprise pregnant women of thepotential hazard to a fetus and the potential risk for loss of the pregnancy. Advisefemales of reproductive potential to use effective contraception during treatment andfor 6 months following the last dose of Lynparza. Based on findings from genetic

‘OP150’ on one side and plain on the reverse side.100 mg: yellow to dark yellow, oval, bi-convex, film-coated, with debossment‘OP100’ on one side and plain on the reverse side.

toxicity and animal reproduction studies, advise male patients with female partners ofreproductive potential or who are pregnant to use effective contraception duringtreatment and for 3 months following the last dose of Lynparza [see Use in SpecificPopulations (8.1, 8.3)].

5.4 Venous Thromboembolic EventsVenous thromboembolic events, including pulmonary embolism, occurred in 7% ofpatients with metastatic castration resistant prostate cancer who received Lynparzaplus androgen deprivation therapy (ADT) compared to 3.1% of patients receivingenzalutamide or abiraterone plus ADT in the PROfound study. Patients receivingLynparza and ADT had a 6% incidence of pulmonary embolism compared to 0.8% ofpatients treated with ADT plus either enzalutamide or abiraterone. Monitor patients forsigns and symptoms of venous thrombosis and pulmonary embolism and treat asmedically appropriate, which may include long-term anticoagulation as clinically indicated.

6 ADVERSE REACTIONSThe following adverse reactions are discussed elsewhere in the labeling:

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6.1 Clinical Trial ExperienceBecause clinical trials are conducted under widely varying conditions, adverse reactionrates observed in the clinical trials of a drug cannot be directly compared to rates in theclinical trials of another drug and may not reflect the rates observed in practice.The data described in the WARNINGS AND PRECAUTIONS reflect exposure to Lynparzaas a single agent in 2901 patients; 2135 patients with exposure to 300 mg twice dailytablet dose including five controlled, randomized, trials (SOLO-1, SOLO-2, OlympiAD,POLO, and PROfound) and to 400 mg twice daily capsule dose in 766 patients in othertrials that were pooled to conduct safety analyses. In these trials, 56% of patients wereexposed for 6 months or longer and 28% were exposed for greater than one year in theLynparza group.In this pooled safety population, the most common adverse reactions in ≥10% ofpatients were nausea (60%), fatigue (55%), anemia (36%), vomiting (32%), diarrhea(24%), decreased appetite (22%), headache (16%), dysgeusia (15%), cough (15%),neutropenia (14%), dyspnea (14%), dizziness (12%), dyspepsia (12%), leukopenia(11%), and thrombocytopenia (10%).First-Line Maintenance Treatment of BRCA-mutated Advanced Ovarian CancerSOLO-1

The safety of Lynparza for the maintenance treatment of patients with BRCA-mutatedadvanced ovarian cancer following first-line treatment with platinum-basedchemotherapy was investigated in SOLO-1 [see Clinical Studies (14.1)]. Patients receivedLynparza tablets 300 mg orally twice daily (n=260) or placebo (n=130) until disease

Myelodysplastic Syndrome/Acute Myeloid Leukemia [see Warnings and Precautions(5.1)]Pneumonitis [see Warnings and Precautions (5.2)]Venous Thromboembolic Events [see Warnings and Precautions (5.4)]

progression or unacceptable toxicity. The median duration of study treatment was 25months for patients who received Lynparza and 14 months for patients who receivedplacebo.Among patients who received Lynparza, dose interruptions due to an adverse reactionof any grade occurred in 52% and dose reductions due to an adverse reaction occurredin 28%. The most frequent adverse reactions leading to dose interruption or reductionof Lynparza were anemia (23%), nausea (14%), and vomiting (10%). Discontinuationdue to adverse reactions occurred in 12% of patients receiving Lynparza. The mostfrequent adverse reactions that led to discontinuation of Lynparza were fatigue (3.1%),anemia (2.3%), and nausea (2.3%).Tables 2 and 3 summarize adverse reactions and laboratory abnormalities in SOLO-1.

Table 2 Adverse Reactions in SOLO-1 (≥10% of Patients Who ReceivedLynparza)

Adverse Reaction Lynparza tablets n=260

Placebo n=130

AllGrades

(%)

Grades 3 – 4(%)

All Grades

(%)

Grades 3 – 4(%)

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Gastrointestinal Disorders Nausea 77 1 38 0 Abdominal pain 45 2 35 1 Vomiting 40 0 15 1 Diarrhea 37 3 26 0 Constipation 28 0 19 0 Dyspepsia 17 0 12 0 Stomatitis 11 0 2 0General Disorders and Administration Site Conditions Fatigue 67 4 42 2Blood and Lymphatic System Disorders Anemia 38 21 9 2 Neutropenia 17 6 7 3 Leukopenia 13 3 8 0 Thrombocytopenia 11 1 4 2Infections and Infestations Upper respiratory tract infection/influenza/nasopharyngitis/bronchitis

28 0 23 0

UTI 13 1 7 0Nervous System Disorders Dysgeusia 26 0 4 0 Dizziness 20 0 15 1Metabolism and Nutrition Disorders Decreased appetite 20 0 10 0Respiratory, Thoracic and Mediastinal Disorders Dyspnea 15 0 6 0

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Graded according to the National Cancer Institute Common Terminology Criteria for AdverseEvents (NCI CTCAE), version 4.0.Includes abdominal pain, abdominal pain lower, abdominal pain upper, abdominal distension,abdominal discomfort, and abdominal tenderness.Includes colitis, diarrhea, and gastroenteritis.

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In addition, the adverse reactions observed in SOLO-1 that occurred in <10% ofpatients receiving Lynparza were increased blood creatinine (8%), lymphopenia (6%),hypersensitivity (2%), MDS/AML (1%), dermatitis (1%), and increased mean cell volume(0.4%).

Table 3 Laboratory Abnormalities Reported in ≥25% of Patients in SOLO-1

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LaboratoryParameter

Lynparza tabletsn =260

Placebon =130

Grades 1-4

(%)

Grades 3-4

(%)

Grades1-4(%)

Grades3-4(%)

Decrease in hemoglobin 87 19 63 2Increase in mean corpuscular volume 87 - 43 -Decrease in leukocytes 70 7 52 1Decrease in lymphocytes 67 14 29 5Decrease in absolute neutrophil count 51 9 38 6Decrease in platelets 35 1 20 2Increase in serum creatinine 34 0 18 0

First-line Maintenance Treatment of HRD-positive Advanced Ovarian Cancerin Combination with BevacizumabPAOLA-1

The safety of Lynparza in combination with bevacizumab for the maintenance treatmentof patients with advanced ovarian cancer following first-line treatment containingplatinum-based chemotherapy and bevacizumab was investigated in PAOLA-1 [seeClinical Studies (14.2)]. This study was a placebo-controlled, double-blind study in which802 patients received either Lynparza 300 mg BID in combination with bevacizumab(n=535) or placebo in combination with bevacizumab (n=267) until disease progressionor unacceptable toxicity. The median duration of treatment with Lynparza was 17.3months and 11 months for bevacizumab post-randomization on theLynparza/bevacizumab arm.Fatal adverse reactions occurred in 1 patient due to concurrent pneumonia and aplasticanemia. Serious adverse reactions occurred in 31% of patients who receivedLynparza/bevacizumab. Serious adverse reactions in >5% of patients includedhypertension (19%) and anemia (17%).

Includes colitis, diarrhea, and gastroenteritis.Includes stomatitis, aphthous ulcer; and mouth ulceration.Includes asthenia, fatigue, lethargy, and malaise.Includes neutropenia, and febrile neutropenia.Includes leukopenia, and white blood cell count decreased.Includes platelet count decreased, and thrombocytopenia.Includes urosepsis, urinary tract infection, urinary tract pain, and pyuria.Includes dyspnea, and dyspnea exertional.

Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.This number represents the safety population. The derived values in the table are based on thetotal number of evaluable patients for each laboratory parameter.

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Dose interruptions due to an adverse reaction of any grade occurred in 54% of patientsreceiving Lynparza/bevacizumab and dose reductions due to an adverse reactionoccurred in 41% of patients who received Lynparza/bevacizumab.The most frequent adverse reactions leading to dose interruption in theLynparza/bevacizumab arm were anemia (21%), nausea (7%), vomiting (3%), andfatigue (3%), and the most frequent adverse reactions leading to reduction in theLynparza/bevacizumab arm were anemia (19%), nausea (7%), and fatigue (4%).Discontinuation due to adverse reactions occurred in 20% of patients receivingLynparza/bevacizumab. Specific adverse reactions that most frequently led todiscontinuation in patients treated with Lynparza/bevacizumab were anemia (4%) andnausea (3%).Tables 4 and 5 summarize adverse reactions and laboratory abnormalities in PAOLA-1,respectively.

Table 4 Adverse Reactions Occurring in ≥10% of Patients Treated withLynparza/bevacizumab in PAOLA-1 and at ≥5% Frequency Compared to the

Placebo/bevacizumab Arm

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Adverse Reactions Lynparza/bevacizumabn=535

Placebo/bevacizumab n=267

Grades 1-4(%)

Grades 3-4(%)

Grades 1-4(%)

Grades 3-4(%)

General Disorders and Administration Site Conditions Fatigue (including asthenia) 53 5 32 1.5Gastrointestinal Disorders Nausea 53 2.4 22 0.7 Vomiting 22 1.7 11 1.9Blood and Lymphatic Disorders Anemia 41 17 10 0.4 Lymphopenia 24 7 9 1.1 Leukopenia 18 1.9 10 1.5

The most common adverse reactions (≥ 10%) for patients receivingLynparza/bevacizumab irrespective of the frequency compared with theplacebo/bevacizumab arm were nausea (53%), fatigue (including asthenia) (53%),anemia (41%), lymphopenia (24%), vomiting (22%), diarrhea (18%), neutropenia (18%),leukopenia (18%), urinary tract infection (15%), and headache (14%).The adverse reactions that occurred in <10% of patients receivingLynparza/bevacizumab were dysgeusia (8%), dyspnea (8%), stomatitis (5%), dyspepsia

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Graded according to the National Cancer Institute Common Terminology Criteria for AdverseEvents (NCI CTCAE), version 4.0.Includes asthenia, and fatigue.Includes anemia, anemia macrocytic, erythropenia, haematocrit decreased, haemoglobindecreased, normochromic anemia, normochromic normocytic anemia, normocytic anemia, andred blood cell count decreased.Includes B-lymphocyte count decreased, lymphocyte count decreased, lymphopenia, and T-lymphocyte count decreased.Includes leukopenia, and white blood cell count decreased.

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(4.3%), erythema (3%), dizziness (2.6%), hypersensitivity (1.7%) and MDS/AML (0.7%).In addition, venous thromboembolic events occurred more commonly in patientsreceiving Lynparza/bevacizumab (5%) than in those receiving placebo/bevacizumab(1.9%).

Table 5 Laboratory Abnormalities Reported in ≥25% of Patients in PAOLA-1

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Laboratory Parameter Lynparza/bevacizumabn =535

Placebo/bevacizumabn =267

Grades 1-4(%)

Grades 3-4(%)

Grades 1-4

(%)

Grades 3-4

(%)Decrease in hemoglobin 79 13 55 0.4Decrease in lymphocytes 63 10 42 3.0Increase in serum creatinine 61 0.4 36 0.4Decrease in leukocytes 59 3.4 45 2.2Decrease in absolute neutrophil count 35 7 30 3.7Decrease in platelets 35 2.4 28 0.4

Maintenance Treatment of Recurrent Ovarian CancerSOLO-2

The safety of Lynparza for the maintenance treatment of patients with platinum sensitivegBRCAm ovarian cancer was investigated in SOLO-2 [see Clinical Studies (14.3)]. Patientsreceived Lynparza tablets 300 mg orally twice daily (n=195) or placebo (n=99) untildisease progression or unacceptable toxicity. The median duration of study treatmentwas 19.4 months for patients who received Lynparza and 5.6 months for patients whoreceived placebo.Among patients who received Lynparza, dose interruptions due to an adverse reactionof any grade occurred in 45% and dose reductions due to an adverse reaction occurredin 27%. The most frequent adverse reactions leading to dose interruption or reductionof Lynparza were anemia (22%), neutropenia (9%), and fatigue/asthenia (8%).Discontinuation due to an adverse reaction occurred in 11% of patients receivingLynparza.Tables 6 and 7 summarize adverse reactions and laboratory abnormalities in SOLO-2.

Table 6 Adverse Reactions in SOLO-2 (≥20% of Patients Who ReceivedLynparza)

Adverse Reaction Lynparza tabletsn=195

Placebon=99

Grades 1-4

(%)

Grades 3-4

(%)

Grades 1-4

(%)

Grades 3-4

(%)

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Reported within 30 days of the last dose.Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.This number represents the safety population. The derived values in the table are based on thetotal number of evaluable patients for each laboratory parameter.

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Gastrointestinal Disorders Nausea 76 3 33 0 Vomiting 37 3 19 1 Diarrhea 33 2 22 0 Stomatitis 20 1 16 0General Disorders and Administration Site Conditions Fatigue including asthenia 66 4 39 2Blood and Lymphatic Disorders Anemia 44 20 9 2Infections and Infestations Nasopharyngitis/URI/sinusitis/rhinitis/influenza

36 0 29 0

Musculoskeletal and Connective Tissue Disorders Arthralgia/myalgia 30 0 28 0Nervous System Disorders Dysgeusia 27 0 7 0 Headache 26 1 14 0Metabolism and Nutrition Disorders Decreased appetite 22 0 11 0

In addition, the adverse reactions observed in SOLO-2 that occurred in <20% ofpatients receiving Lynparza were neutropenia (19%), cough (18%), leukopenia (16%),hypomagnesemia (14%), thrombocytopenia (14%), dizziness (13%), dyspepsia (11%),increased creatinine (11%), MDS/AML (8%), edema (8%), rash (6%), and lymphopenia(1%).

Table 7 Laboratory Abnormalities Reported in ≥25% of Patients in SOLO-2Laboratory Parameter Lynparza tablets

n =195Placebon =99

Grades 1-4(%)

Grades 3-4(%)

Grades 1-4(%)

Grades 3-4(%)

Increase in meancorpuscular volume

89 - 52 -

Decrease in hemoglobin 83 17 69 0Decrease in leukocytes 69 5 48 1Decrease in lymphocytes 67 11 37 1Decrease in absoluteneutrophil count

51 7 34 3

Increase in serum creatinine 44 0 29 0

Graded according to the National Cancer Institute Common Terminology Criteria for AdverseEvents (NCI CTCAE), version 4.0.Represents grouped term consisting of abscess oral, aphthous ulcer, gingival abscess, gingivaldisorder, gingival pain, gingivitis, mouth ulceration, mucosal infection, mucosal inflammation, oralcandidiasis, oral discomfort, oral herpes, oral infection, oral mucosal erythema, oral pain,oropharyngeal discomfort, and oropharyngeal pain.Represents grouped term consisting of anemia, hematocrit decreased, hemoglobin decreased,iron deficiency, mean cell volume increased and red blood cell count decreased.

†

‡

*† †

‡

*†

‡

Decrease in platelets 42 2 22 1

Study 19

The safety of Lynparza as maintenance monotherapy was evaluated in patients withplatinum sensitive ovarian cancer who had received 2 or more previous platinumcontaining regimens in Study 19 [see Clinical Studies (14.3)]. Patients received Lynparzacapsules 400 mg orally twice daily (n=136) or placebo (n=128). At the time of finalanalysis, the median duration of exposure was 8.7 months in patients who receivedLynparza and 4.6 months in patients who received placebo.Adverse reactions led to dose interruptions in 35% of patients receiving Lynparza; dosereductions in 26% and discontinuation in 6% of patients receiving Lynparza.Tables 8 and 9 summarize adverse reactions and laboratory abnormalities in Study 19.

Table 8 Adverse Reactions in Study 19 (≥20% of Patients Who ReceivedLynparza)

*†

Adverse Reaction Lynparza capsulesn=136

Placebon=128

Grades 1-4

(%)

Grades 3-4

(%)

Grades 1-4(%)

Grades 3-4(%)

Gastrointestinal Disorders Nausea 71 2 36 0 Vomiting 35 2 14 1 Diarrhea 28 2 25 2 Constipation 22 1 12 0 Dyspepsia 20 0 9 0General Disorders and Administration Site Conditions Fatigue (including asthenia) 63 9 46 3Blood and Lymphatic Disorders Anemia 23 7 7 1Infections and Infestations Respiratory tract infection 22 2 11 0Metabolism and Nutrition Disorders Decreased appetite 21 0 13 0Nervous System Disorders Headache 21 0 13 1

In addition, the adverse reactions in Study 19 that occurred in <20% of patients

Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.This number represents the safety population. The derived values in the table are based on thetotal number of evaluable patients for each laboratory parameter.Represents the proportion of subjects whose mean corpuscular volume was > upper limit ofnormal (ULN).

*

Graded according to NCI CTCAE v4.0.Represents grouped terms of related terms that reflect the medical concept of the adversereaction.

†

receiving Lynparza were dysgeusia (16%), dizziness (15%), dyspnea (13%), pyrexia(10%), stomatitis (9%), edema (9%), increase in creatinine (7%), neutropenia (5%),thrombocytopenia (4%), leukopenia (2%), MDS/AML (1%) and lymphopenia (1%).

Table 9 Laboratory Abnormalities Reported in ≥25% of Patients in Study 19

*†

‡

Laboratory Parameter Lynparza capsulesn =136

Placebon =129

Grades 1-4(%)

Grades 3-4(%)

Grades 1-4(%)

Grades 3-4(%)

Decrease in hemoglobin 82 8 58 1Increase in mean corpuscularvolume

82 - 51 -

Decrease in leukocytes 58 4 37 2Decrease in lymphocytes 52 10 32 3Decrease in absoluteneutrophil count

47 7 40 2

Increase in serum creatinine 45 0 14 0Decrease in platelets 36 4 18 0

Advanced Germline BRCA-mutated Ovarian Cancer After 3 or More Lines ofChemotherapyPooled Data

The safety of Lynparza was investigated in 223 patients (pooled from 6 studies) withgBRCAm advanced ovarian cancer who had received 3 or more prior lines ofchemotherapy [see Clinical Studies (14.4)]. Patients received Lynparza capsules 400 mgorally twice daily until disease progression or unacceptable tolerability. The medianexposure to Lynparza in these patients was 5.2 months.There were 8 (4%) patients with adverse reactions leading to death, two were attributedto acute leukemia, and one each was attributed to COPD, cerebrovascular accident,intestinal perforation, pulmonary embolism, sepsis, and suture rupture. Adversereactions led to dose interruption in 40% of patients, dose reduction in 4%, anddiscontinuation in 7%.Tables 10 and 11 summarize the adverse reactions and laboratory abnormalities fromthe pooled studies.

Table 10 Adverse Reactions Reported in Pooled Data (≥20% of Patients WhoReceived Lynparza)

Adverse Reaction Lynparza capsulesn=223

Grades 1-4(%)

Grades 3-4(%)

Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.This number represents the safety population. The derived values in the table are based on thetotal number of evaluable patients for each laboratory parameter.Represents the proportion of subjects whose mean corpuscular volume was > ULN.

*† †

‡

General Disorders Fatigue/asthenia 66 8Gastrointestinal Disorders Nausea 64 3 Vomiting 43 4 Diarrhea 31 1 Dyspepsia 25 0 Decreased appetite 22 1Blood and Lymphatic Disorders Anemia 34 18Infections and Infestations Nasopharyngitis/URI 26 0Musculoskeletal and Connective Tissue Disorders Arthralgia/musculoskeletal pain 21 0 Myalgia 22 0

Table 11 Laboratory Abnormalities Reported in ≥25% of Patients in PooledData

*†

Laboratory Parameter Lynparza capsulesn =223

Grades 1-4(%)

Grades 3-4(%)

Decrease in hemoglobin 90 15Mean corpuscular volume elevation 57 -Decrease in lymphocytes 56 17Decrease in platelets 30 3Increase in creatinine 30 2Decrease in absolute neutrophil count 25 7

The following adverse reactions and laboratory abnormalities have been identified in ≥10to <20% of the 223 patients receiving Lynparza and not included in the table: cough(16%), constipation (16%), dysgeusia (16%), headache (15%), peripheral edema (14%),back pain (14%), urinary tract infection (14%), dyspnea (13%), and dizziness (11%).The following adverse reactions and laboratory abnormalities have been identified in<10% of the 223 patients receiving Lynparza and not included in the table: leukopenia(9%), pyrexia (8%), peripheral neuropathy (5%), hypomagnesemia (5%), rash (5%),stomatitis (4%), MDS/AML (1.8%), and venous thrombosis (including pulmonaryembolism) (1%).Germline BRCA-mutated HER2-negative Metastatic Breast CancerOlympiAD

The safety of Lynparza was evaluated in gBRCAm patients with HER2-negativemetastatic breast cancer who had previously received up to two lines of chemotherapy

Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.This number represents the safety population. The derived values in the table are based on thetotal number of evaluable patients for each laboratory parameter.

*†

for the treatment of metastatic disease in OlympiAD [see Clinical Studies (14.5)]. Patientsreceived either Lynparza tablets 300 mg orally twice daily (n=205) or a chemotherapy(capecitabine, eribulin, or vinorelbine) of the healthcare provider’s choice (n=91) untildisease progression or unacceptable toxicity. The median duration of study treatmentwas 8.2 months in patients who received Lynparza and 3.4 months in patients whoreceived chemotherapy.Among patients who received Lynparza, dose interruptions due to an adverse reactionof any grade occurred in 35% and dose reductions due to an adverse reaction occurredin 25%. Discontinuation due to an adverse reaction occurred in 5% of patients receivingLynparza.Tables 12 and 13 summarize the adverse reactions and laboratory abnormalities inOlympiAD.

Table 12 Adverse Reactions in OlympiAD (≥20% of Patients Who ReceivedLynparza)

*†

‡

§

¶

Adverse Reaction Lynparza tabletsn=205

Chemotherapyn=91

Grades 1-4

(%)

Grades 3-4

(%)

Grades 1-4(%)

Grades 3-4(%)

Gastrointestinal Disorders Nausea 58 0 35 1 Vomiting 30 0 15 1 Diarrhea 21 1 22 0Blood and Lymphatic Disorders Anemia 40 16 26 4 Neutropenia 27 9 50 26 Leukopenia 25 5 31 13General Disorders and Administration Site Conditions Fatigue (including asthenia) 37 4 36 1Infections and Infestations Respiratory tract infection 27 1 22 0Nervous System Disorders Headache 20 1 15 2

In addition, adverse reactions in OlympiAD that occurred in <20% of patients receivingLynparza were cough (18%), decreased appetite (16%), thrombocytopenia (11%),

*

Graded according to NCI CTCAE v4.0.Represents grouped terms consisting of anemia (anemia erythropenia, hematocrit decreased,hemoglobin decreased and red blood cell count decreased).Represents grouped terms consisting of neutropenia (febrile neutropenia, granulocyte countdecreased, granulocytopenia, neutropenia, neutropenic infection, neutropenic sepsis, andneutrophil count decreased).Represents grouped terms consisting of leukopenia (leukopenia and white blood cell countdecreased).Represents grouped terms consisting of bronchitis, influenza, lower respiratory tract infection,nasopharyngitis, pharyngitis, respiratory tract infection, rhinitis, sinusitis, upper respiratory tractinfection, and upper respiratory tract infection bacterial.

†‡

§

¶

dysgeusia (9%), lymphopenia (8%), dyspepsia (8%), dizziness (7%), stomatitis (7%),upper abdominal pain (7%), rash (5%), increase in serum creatinine (3%), and dermatitis(1%).

Table 13 Laboratory Abnormalities Reported in ≥25% of Patients in OlympiAD

*†

‡

Laboratory Parameter

Lynparza tabletsn = 205

Chemotherapyn = 91

Grades 1-4

(%)

Grades 3-4(%)

Grades 1-4(%)

Grades 3-4

(%)Decrease in hemoglobin 82 17 66 3Decrease in lymphocytes 73 21 63 3Decrease in leukocytes 71 8 70 23Increase in mean corpuscularvolume

71 - 33 -

Decrease in absolute neutrophilcount

46 11 65 38

Decrease in platelets 33 3 28 0

First-line Maintenance Treatment of Germline BRCA-mutated Metastatic PancreaticAdenocarcinomaPOLO

The safety of Lynparza as maintenance treatment of germline BRCA-mutated metastaticpancreatic adenocarcinoma following first-line treatment with platinum-basedchemotherapy was evaluated in POLO [see Clinical Studies (14.6)]. Patients receivedLynparza tablets 300 mg orally twice daily (n=90) or placebo (n=61) until diseaseprogression or unacceptable toxicity. Among patients receiving Lynparza, 34% wereexposed for 6 months or longer and 25% were exposed for greater than one year.Among patients who received Lynparza, dosage interruptions due to an adversereaction of any grade occurred in 35% and dosage reductions due to an adversereaction occurred in 17%. The most frequent adverse reactions leading to dosageinterruption or reduction in patients who received Lynparza were anemia (11%),vomiting (5%), abdominal pain (4%), asthenia (3%), and fatigue (2%). Discontinuationdue to adverse reactions occurred in 6% of patients receiving Lynparza. The mostfrequent adverse reaction that led to discontinuation of Lynparza was fatigue (2.2%).Tables 14 and 15 summarize the adverse reactions and laboratory abnormalities inpatients in POLO.

Table 14 Adverse Reactions in POLO (Occurring in ≥10% of Patients whoReceived Lynparza)

Adverse Reaction Lynparza tablets Placebo

Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.This number represents the safety population. The derived values in the table are based on thetotal number of evaluable patients for each laboratory parameter.Represents the proportion of subjects whose mean corpuscular volume was > ULN.

*† †

‡

*

† †

(n=91) (n=60)All Grades

(%)Grades 3 – 4 (%)

All Grades

(%)

Grades 3 – 4 (%)

*†

‡§¶#Þßà

General Disorders and Administration Site Conditions Fatigue 60 5 35 2Gastrointestinal Disorders Nausea 45 0 23 2 Abdominal pain 34 2 37 5 Diarrhea 29 0 15 0 Constipation 23 0 10 0 Vomiting 20 1 15 2 Stomatitis 10 0 5 0Blood and Lymphatic System Disorders Anemia 27 11 17 3 Thrombocytopenia 14 3 7 0 Neutropenia 12 4 8 3Metabolism and Nutrition Disorders Decreased appetite 25 3 7 0Musculoskeletal and Connective Tissue Disorders Back pain 19 0 17 2 Arthralgia 15 1 10 0Skin and Subcutaneous Tissue Disorder Rash 15 0 5 0Respiratory, Thoracic and Mediastinal Disorders Dyspnea 13 0 5 2Infections and Infestations Nasopharyngitis 12 0 3 0Nervous System Disorders Dysgeusia 11 0 5 0

In addition, the adverse reactions observed in POLO that occurred in <10% of patientsreceiving Lynparza were cough (9%), abdominal pain upper (7%), blood creatinineincreased (7%), dizziness (7%), headache (7%), dyspepsia (5%), leukopenia (5%),hypersensitivity (2%), and lymphopenia (2%).

Table 15 Laboratory Abnormalities Reported in ≥25% of Patients in POLOLaboratoryParameter

Lynparza tabletsn =91

Placebon =60

Grades 1-4(%)

Grades3-4

Grades1-4 (%)

Grades3-4

† †

Graded according to NCI CTCAE, version 4.0This number represents the safety population. The derived values in the table are based on thetotal number of evaluable patients for each laboratory parameter.Includes asthenia and fatigueIncludes abdominal pain, abdominal pain upper, abdominal pain lowerIncludes stomatitis and mouth ulcerationIncludes platelets count decreased and thrombocytopeniaIncludes neutropenia, febrile neutropenia and neutrophil count decreasedIncludes rash erythematous, rash macular and rash maculo-papularIncludes dyspnea and dyspnea exertional

‡

§

¶

#Þ

ß

à

* † †

*

†

‡

(%) (%)Increase in serum creatinine 99 2 85 0Decrease in hemoglobin 86 11 65 0Increase in mean corpuscular volume 71 - 30 -Decrease in lymphocytes 61 9 27 0Decrease in platelets 56 2 39 0Decrease in leukocytes 50 3 23 0Decrease in absolute neutrophil count 25 3 10 0

HRR Gene-mutated Metastatic Castration-Resistant Prostate CancerPROfound

The safety of Lynparza as monotherapy was evaluated in patients with mCRPC and HRRgene mutations who have progressed following prior treatment with enzalutamide orabiraterone in PROfound [see Clinical Studies (14.7)]. This study was a randomized,open-label, multi-center study in which 386 patients received either Lynparza tablets 300mg orally twice daily (n=256) or investigator’s choice of enzalutamide or abirateroneacetate (n=130) until disease progression or unacceptable toxicity. Among patientsreceiving Lynparza, 62% were exposed for 6 months or longer and 20% were exposedfor greater than one year.Fatal adverse reactions occurred in 4% of patients treated with Lynparza. Theseincluded pneumonia (1.2%), cardiopulmonary failure (0.4%), aspiration pneumonia(0.4%), intestinal diverticulum (0.4%), septic shock (0.4%), Budd-Chiari Syndrome(0.4%), sudden death (0.4%), and acute cardiac failure (0.4%).Serious adverse reactions occurred in 36% of patients receiving Lynparza. The mostfrequent serious adverse reactions (≥2%) were anemia (9%), pneumonia (4%),pulmonary embolism (2%), fatigue/asthenia (2%), and urinary tract infection (2%).Dose interruptions due to an adverse reaction of any grade occurred in 45% of patientsreceiving Lynparza; dose reductions due to an adverse reaction occurred in 22% ofLynparza patients. The most frequent adverse reactions leading to dose interruption ofLynparza were anemia (25%) and thrombocytopenia (6%) and the most frequentadverse reaction leading to reduction of Lynparza was anemia (16%). Discontinuationdue to adverse reactions occurred in 18% of Lynparza. The adverse reaction that mostfrequently led to discontinuation of Lynparza was anemia (7%).Tables 16 and 17 summarize the adverse reactions and laboratory abnormalities,respectively, in patients in PROfound.

Table 16 Adverse Reactions Reported in ≥10% of Patients in PROfoundAdverse Reactions Lynparza tablets

n=256Enzalutamide or

abirateronen=130

Patients were allowed to enter POLO with hemoglobin ≥9 g/dL (CTCAE Grade 2) and otherlaboratory values of CTCAE Grade 1.This number represents the safety population. The derived values in the table are based on thetotal number of evaluable patients for each laboratory parameter.Represents the proportion of subjects whose mean corpuscular volume was > ULN.

‡

*

*

†‡

Grades 1-4(%)

Grades 3-4(%)

Grades 1-4(%)

Grades 3-4(%)

Blood and lymphatic disorders Anemia 46 21 15 5 Thrombocytopenia 12 4 3 0Gastrointestinal disorders Nausea 41 1 19 0 Diarrhea 21 1 7 0 Vomiting 18 2 12 1General disorders and administration site conditions Fatigue (including asthenia) 41 3 32 5Metabolism and nutrition disorders Decreased appetite 30 1 18 1Respiratory, thoracic, and mediastinal disorders Cough 11 0 2 0 Dyspnea 10 2 3 0

In addition, adverse reactions of clinical relevance in PROfound that occurred in <10% ofpatients receiving Lynparza were neutropenia (9%), venous thromboembolic events(7%), dizziness (7%), dysgeusia (7%), dyspepsia (7%), headache (6%), pneumonia (5%),stomatitis (5%), rash (4%), blood creatinine increase (4%), pneumonitis (2%), upperabdominal pain (2%), and hypersensitivity (1%).

Table 17 Laboratory Abnormalities Reported in ≥25% of Patients in PROfound

*†

LaboratoryParameter

Lynparza tabletsn = 256

Enzalutamide orabiraterone

n =130Grades 1-4n= 247 (%)

Grades 3-4

n=247 (%)

Grades 1-4n=124 (%)

Grades 3-4n=124 (%)

Decrease in hemoglobin 242 (98) 33 (13) 91 (73) 5 (4)Decrease in lymphocytes 154 (62) 57 (23) 42 (34) 16 (13)Decrease in leukocytes 130 (53) 9 (4) 26 (21) 0Decrease in absolute neutrophilcount

83 (34) 8 (3) 11 (9) 0

6.2 Postmarketing ExperienceThe following adverse reactions have been identified during post approval use ofLynparza. Because these reactions are reported voluntarily from a population ofuncertain size, it is not always possible to reliably estimate their frequency or establish a

Graded according to the National Cancer Institute Common Terminology Criteria for AdverseEvents (NCI CTCAE), version 4.03Includes anemia and hemoglobin decreasedIncludes platelet count decreased and thrombocytopenia

†‡

Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.This number represents the safety population. The derived values in the table are based on thetotal number of evaluable patients for each laboratory parameter.

*

††

causal relationship to drug exposure.Immune System Disorders: Hypersensitivity including angioedema.Skin and subcutaneous tissue disorders: Erythema nodosum, rash, dermatitis.

7 DRUG INTERACTIONS

7.1 Use with Anticancer AgentsClinical studies of Lynparza with other myelosuppressive anticancer agents, includingDNA damaging agents, indicate a potentiation and prolongation of myelosuppressivetoxicity.

7.2 Effect of Other Drugs on LynparzaStrong and Moderate CYP3A InhibitorsCoadministration of CYP3A inhibitors can increase olaparib concentrations, which mayincrease the risk for adverse reactions [see Clinical Pharmacology (12.3)]. Avoidcoadministration of strong or moderate CYP3A inhibitors. If the strong or moderateinhibitor must be coadministered, reduce the dose of Lynparza [see Dosage andAdministration (2.4)].

Strong and Moderate CYP3A InducersConcomitant use with a strong or moderate CYP3A inducer decreased olaparibexposure, which may reduce Lynparza efficacy [see Clinical Pharmacology (12.3)]. Avoidcoadministration of strong or moderate CYP3A inducers.

8 USE IN SPECIFIC POPULATIONS

8.1 PregnancyRisk SummaryBased on findings in animals and its mechanism of action [see Clinical Pharmacology(12.1)], Lynparza can cause fetal harm when administered to a pregnant woman. Thereare no available data on Lynparza use in pregnant women to inform the drug-associatedrisk. In an animal reproduction study, the administration of olaparib to pregnant ratsduring the period of organogenesis caused teratogenicity and embryo-fetal toxicity atexposures below those in patients receiving the recommended human dose of 300 mgtwice daily (see Data). Apprise pregnant women of the potential hazard to the fetus andthe potential risk for loss of the pregnancy.The estimated background risk of major birth defects and miscarriage for the indicatedpopulation is unknown. The estimated background risk in the U.S. general population ofmajor birth defects is 2-4%; and the risk for spontaneous abortion is approximately 15-20% in clinically recognized pregnancies.

DataAnimal Data

In a fertility and early embryonic development study in female rats, olaparib wasadministered orally for 14 days before mating through to Day 6 of pregnancy, whichresulted in increased post-implantation loss at a dose level of 15 mg/kg/day (withmaternal systemic exposures approximately 7% of the human exposure (AUC ) atthe recommended dose).In an embryo-fetal development study, pregnant rats received oral doses of 0.05 and0.5 mg/kg/day olaparib during the period of organogenesis. A dose of 0.5 mg/kg/day(with maternal systemic exposures approximately 0.18% of human exposure (AUC )at the recommended dose) caused embryo-fetal toxicities including increased post-implantation loss and major malformations of the eyes (anophthalmia, microphthalmia),vertebrae/ribs (extra rib or ossification center; fused or absent neural arches, ribs, andsternebrae), skull (fused exoccipital), and diaphragm (hernia). Additional abnormalities orvariants included incomplete or absent ossification (vertebrae/sternebrae, ribs, limbs)and other findings in the vertebrae/sternebrae, pelvic girdle, lung, thymus, liver, ureter,and umbilical artery. Some findings noted above in the eyes, ribs, and ureter wereobserved at a dose of 0.05 mg/kg/day olaparib at lower incidence.

8.2 LactationRisk SummaryNo data are available regarding the presence of olaparib in human milk, or on its effectson the breastfed infant or on milk production. Because of the potential for seriousadverse reactions in the breastfed infants from Lynparza, advise a lactating woman notto breastfeed during treatment with Lynparza and for one month after receiving the lastdose.

8.3 Females and Males of Reproductive PotentialPregnancy TestingRecommend pregnancy testing for females of reproductive potential prior to initiatingtreatment with Lynparza.ContraceptionFemales

Lynparza can cause fetal harm when administered to a pregnant woman [see Use inSpecific Populations (8.1)]. Advise females of reproductive potential to use effectivecontraception during treatment with Lynparza and for at least 6 months following thelast dose.Males

Based on findings in genetic toxicity and animal reproduction studies, advise malepatients with female partners of reproductive potential or who are pregnant to useeffective contraception during treatment and for 3 months following the last dose ofLynparza. Advise male patients not to donate sperm during therapy and for 3 monthsfollowing the last dose of Lynparza [see Use in Specific Populations (8.1) and NonclinicalToxicology (13.1)].

8.4 Pediatric Use

0-24h

0-24h

Safety and effectiveness of Lynparza have not been established in pediatric patients.

8.5 Geriatric UseOf the 2351 patients with advanced solid tumors who received Lynparza tablets 300 mgorally twice daily as monotherapy, 596 (25%) patients were aged ≥65 years, and thisincluded 137 (6%) patients who were aged ≥75 years. Seven (0.3%) patients were aged≥85 years.Of the 535 patients with advanced solid tumors who received Lynparza tablets 300 mgorally twice daily in combination with bevacizumab, 204 (38%) patients were aged ≥65years, and this included 31 (6%) patients who were aged ≥75 years.No overall differences in the safety or effectiveness of Lynparza were observed betweenthese patients and younger patients.

8.6 Renal ImpairmentNo dosage modification is recommended in patients with mild renal impairment (CLcr 51to 80 mL/min estimated by Cockcroft-Gault). Reduce Lynparza dosage to 200 mg twicedaily in patients with moderate renal impairment (CLcr 31 to 50 mL/min) [see Dosage andAdministration (2.5)]. There are no data in patients with severe renal impairment or end-stage disease (CLcr ≤30 mL/min) [see Clinical Pharmacology (12.3)].

8.7 Hepatic ImpairmentNo adjustment to the starting dose is required in patients with mild or moderate hepaticimpairment (Child-Pugh classification A and B). There are no data in patients with severehepatic impairment (Child-Pugh classification C) [see Clinical Pharmacology (12.3)].

11 DESCRIPTIONOlaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor. The chemical name is 4-[(3-{[4-(cyclopropylcarbonyl)piperazin-1-yl]carbonyl}-4-fluorophenyl)methyl]phthalazin-1(2H)-one. The empirical molecular formula for Lynparza is C24H23FN4O3 and therelative molecular mass is 434.46. It has the following chemical structure:

Olaparib is a crystalline solid, is non-chiral and shows pH-independent low solubility

across the physiological pH range.Lynparza (olaparib) tablets for oral use contain 100 mg or 150 mg of olaparib. Inactiveingredients in the tablet core are copovidone, mannitol, colloidal silicon dioxide, andsodium stearyl fumarate. The tablet coating consists of hypromellose, polyethyleneglycol 400, titanium dioxide, ferric oxide yellow, and ferrosoferric oxide (150 mg tabletonly).

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of ActionOlaparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, includingPARP1, PARP2, and PARP3. PARP enzymes are involved in normal cellular functions,such as DNA transcription and DNA repair. Olaparib has been shown to inhibit growth ofselect tumor cell lines in vitro and decrease tumor growth in mouse xenograft models ofhuman cancer, both as monotherapy or following platinum-based chemotherapy.Increased cytotoxicity and anti-tumor activity following treatment with olaparib werenoted in cell lines and mouse tumor models with deficiencies in BRCA1/2, ATM, or othergenes involved in the homologous recombination repair (HRR) of DNA damage andcorrelated with platinum response. In vitro studies have shown that olaparib-inducedcytotoxicity may involve inhibition of PARP enzymatic activity and increased formation ofPARP-DNA complexes, resulting in DNA damage and cancer cell death.

12.2 PharmacodynamicsCardiac ElectrophysiologyThe effect of olaparib on cardiac repolarization was assessed in 119 patients following asingle dose of 300 mg and in 109 patients following multiple dosing of 300 mg twicedaily. No clinically relevant effect of olaparib on QT interval was observed.

12.3 PharmacokineticsThe area under the curve (AUC) of olaparib increases approximately proportionallyfollowing administration of single doses of 25 mg to 450 mg (0.08 to 1.5 times therecommended dose) and maximal concentrations (C ) increased slightly less thanproportionally for the same dose range. Olaparib showed time-dependentpharmacokinetics and an AUC mean accumulation ratio of 1.8 is observed at steadystate following a dose of 300 mg twice daily.The mean (CV%) olaparib C is 5.4 μg/mL (32%) and AUC is 39.2 μg*h/mL (44%)following a single 300 mg dose. The mean steady state olaparib C and AUC is 7.6μg/mL (35%) and 49.2 μg*h/mL (44%), following a dose of 300 mg twice daily.AbsorptionFollowing oral administration of olaparib, the median time to peak plasma concentrationis 1.5 hours.Effect of Food

Co-administration of a high fat and high calorie meal (800-1000 kcal, 50% of the caloriecontent made up from fat) with olaparib slowed the rate (t delayed by 2.5 hours) of

max

maxmax

max

absorption, but did not significantly alter the extent of olaparib absorption (mean AUCincreased by approximately 8%).DistributionThe mean (± standard deviation) apparent volume of distribution of olaparib is 158 ±136 L following a single 300 mg dose of Lynparza. The protein binding of olaparib isapproximately 82% in vitro.EliminationThe mean (± standard deviation) terminal plasma half-life of olaparib is 14.9 ± 8.2 hoursand the apparent plasma clearance is 7.4 ± 3.9 L/h following a single 300 mg dose ofLynparza.Metabolism

Olaparib is metabolized by cytochrome P450 (CYP) 3A in vitro.Following an oral dose of radiolabeled olaparib to female patients, unchanged olaparibaccounted for 70% of the circulating radioactivity in plasma. It was extensivelymetabolized with unchanged drug accounting for 15% and 6% of radioactivity in urineand feces, respectively. The majority of the metabolism is attributable to oxidationreactions with a number of the components produced undergoing subsequentglucuronide or sulfate conjugation.Excretion

Following a single dose of radiolabeled olaparib, 86% of the dosed radioactivity wasrecovered within a 7-day collection period, 44% via the urine and 42% via the feces. Themajority of the material was excreted as metabolites.Specific PopulationsPatients with Renal Impairment

In a renal impairment trial, the mean AUC increased by 24% and C by 15%, whenolaparib was dosed in patients with mild renal impairment (CLcr=51-80 mL/min definedby the Cockcroft-Gault equation; n=13) and by 44% and 26%, respectively, whenolaparib was dosed in patients with moderate renal impairment (CLcr=31-50 mL/min;n=13), compared to those with normal renal function (CLcr ≥81 mL/min; n=12). Therewas no evidence of a relationship between the extent of plasma protein binding ofolaparib and creatinine clearance. There are no data in patients with severe renalimpairment or end-stage renal disease (CLcr ≤30 mL/min).Patients with Hepatic Impairment

In a hepatic impairment trial, the mean AUC increased by 15% and the mean Cincreased by 13% when olaparib was dosed in patients with mild hepatic impairment(Child-Pugh classification A; n=10) and the mean AUC increased by 8% and the meanC decreased by 13% when olaparib was dosed in patients with moderate hepaticimpairment (Child-Pugh classification B; n=8), compared to patients with normal hepaticfunction (n=13). Hepatic impairment has no effect on the protein binding of olapariband, therefore, total plasma exposure was representative of free drug. There are nodata in patients with severe hepatic impairment (Child-Pugh classification C).Drug Interaction Studies

max

max

max

max

Clinical Studies

CYP3A Inhibitors: Concomitant use of itraconazole (strong CYP3A inhibitor) increasedolaparib C by 42% and AUC by 170%. Concomitant use of fluconazole (moderateCYP3A inhibitor) is predicted to increase olaparib C by 14% and AUC by 121%.CYP3A Inducers: Concomitant use of rifampicin (strong CYP3A inducer) decreasedolaparib C by 71% and AUC by 87%. Concomitant use of efavirenz (moderate CYP3Ainducer) is predicted to decrease olaparib C by 31% and AUC by 60%.In vitro Studies

CYP Enzymes: Olaparib is both an inhibitor and inducer of CYP3A and an inducer ofCYP2B6. Olaparib is predicted to be a weak CYP3A inhibitor in humans.UGT Enzymes: Olaparib is an inhibitor of UGT1A1.Transporters: Olaparib is an inhibitor of BCRP, OATP1B1, OCT1, OCT2, OAT3, MATE1,and MATE2K. Olaparib is a substrate and inhibitor of the efflux transporter P-gp. Thepotential for olaparib to induce P-gp has not been evaluated.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of FertilityCarcinogenicity studies have not been conducted with olaparib.Olaparib was clastogenic in an in vitro chromosomal aberration assay in mammalianChinese hamster ovary (CHO) cells and in an in vivo rat bone marrow micronucleusassay. This clastogenicity is consistent with genomic instability resulting from theprimary pharmacology of olaparib and indicates potential for genotoxicity in humans.Olaparib was not mutagenic in a bacterial reverse mutation (Ames) test.In a fertility study, female rats received oral olaparib at doses of 0.05, 0.5, and 15mg/kg/day for at least 14 days before mating through the first week of pregnancy.There were no adverse effects on mating and fertility rates at doses up to 15 mg/kg/day(maternal systemic exposures approximately 7% of the human exposure (AUC ) atthe recommended dose).In a male fertility study, olaparib had no effect on mating and fertility in rats at oral dosesup to 40 mg/kg/day following at least 70 days of olaparib treatment (with systemicexposures of approximately 5% of the human exposure (AUC ) at therecommended dose).

14 CLINICAL STUDIES

14.1 First-Line Maintenance Treatment of BRCA-mutated Advanced OvarianCancerThe efficacy of Lynparza was evaluated in SOLO-1 (NCT01844986), a randomized (2:1),double-blind, placebo-controlled, multi-center trial in patients with BRCA-mutatedadvanced ovarian, fallopian tube, or primary peritoneal cancer following first-lineplatinum-based chemotherapy. Patients were randomized to receive Lynparza tablets

maxmax

maxmax

0-24h

0-24h

300 mg orally twice daily or placebo. Treatment was continued for up to 2 years or untildisease progression or unacceptable toxicity; however, patients with evidence of diseaseat 2 years, who in the opinion of the treating healthcare provider could derive furtherbenefit from continuous treatment, could be treated beyond 2 years. Randomizationwas stratified by response to first-line platinum-based chemotherapy (complete orpartial response). The major efficacy outcome was investigator-assessed progression-free survival (PFS) evaluated according to Response Evaluation Criteria in Solid Tumors(RECIST), version 1.1.A total of 391 patients were randomized, 260 to Lynparza and 131 to placebo. Themedian age of patients treated with Lynparza was 53 years (range: 29 to 82) and 53years (range: 31 to 84) among patients on placebo. The ECOG performance status (PS)was 0 in 77% of patients receiving Lynparza and 80% of patients receiving placebo. Ofall patients, 82% were White, 36% were enrolled in the U.S. or Canada, and 82% were incomplete response to their most recent platinum-based regimen. The majority ofpatients (n=389) had germline BRCA mutation (gBRCAm), and 2 patients had somaticBRCAm (sBRCAm).Of the 391 patients randomized in SOLO-1, 386 were retrospectively or prospectivelytested with a Myriad BRACAnalysis test and 383 patients were confirmed to havedeleterious or suspected deleterious gBRCAm status; 253 were randomized to theLynparza arm and 130 to the placebo arm. Two out of 391 patients randomized inSOLO-1 were confirmed to have sBRCAm based on an investigational FoundationMedicine tissue test.SOLO-1 demonstrated a statistically significant improvement in investigator-assessedPFS for Lynparza compared to placebo. Results from a blinded independent review wereconsistent. At the time of the analysis of PFS, overall survival (OS) data were not mature(21% of patients had died). Efficacy results are presented in Table 18 and Figure 1.

Table 18 Efficacy Results - SOLO-1 (Investigator Assessment)

*†

‡

Lynparza tablets(n=260)

Placebo(n=131)

Progression-FreeSurvival Number of events (%) 102 (39%) 96 (73%) Median, months NR 13.8 Hazard ratio (95% CI) 0.30 (0.23, 0.41) p-value <0.0001NR not reached; CI Confidence Interval.

Figure 1 Kaplan-Meier Curves of Investigator-Assessed Progression-FreeSurvival - SOLO-1

Median follow up of 41 months in both treatment arms.A value <1 favors olaparib. Hazard ratio from a Cox proportional hazards model including responseto previous platinum chemotherapy (complete response versus partial response) as a covariate.The p-value is derived from a stratified log-rank test.

*

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14.2 First-line Maintenance Treatment of HRD-positive Advanced OvarianCancer in Combination with BevacizumabPAOLA-1 (NCT02477644) was a randomized, double-blind, placebo-controlled, multi-center trial that compared the efficacy of Lynparza in combination with bevacizumabversus placebo/bevacizumab for the maintenance treatment of advanced high-gradeepithelial ovarian cancer, fallopian tube or primary peritoneal cancer following first-lineplatinum-based chemotherapy and bevacizumab. Randomization was stratified by first-line treatment outcome (timing and outcome of cytoreductive surgery and response toplatinum-based chemotherapy) and tBRCAm status, determined by prospective localtesting. All available clinical samples were retrospectively tested with Myriad myChoiceCDx. Patients were required to have no evidence of disease (NED) due to completesurgical resection, or who were in complete response (CR), or partial response (PR)following completion of first-line platinum-containing chemotherapy and bevacizumab.Patients were randomized (2:1) to receive Lynparza tablets 300 mg orally twice daily incombination with bevacizumab (n=537) 15 mg/kg every three weeks orplacebo/bevacizumab (n=269) Patients continued bevacizumab in the maintenancesetting and started treatment with Lynparza after a minimum of 3 weeks and up to amaximum of 9 weeks following completion of their last dose of chemotherapy. Lynparzatreatment was continued for up to 2 years or until progression of the underlying disease

®

or unacceptable toxicity. Patients who in the opinion of the treating physician couldderive further benefit from continuous treatment could be treated beyond 2 years.Treatment with bevacizumab was for a total of up to 15 months, including the periodgiven with chemotherapy and given as maintenance.The major efficacy outcome measure was investigator-assessed PFS evaluatedaccording to RECIST, version 1.1. An additional efficacy endpoint was overall survival(OS).The median age of patients in both arms was 61 years overall (range 26 to 87). Ovariancancer was the primary tumor type in 86% of patients in both arms. Ninety six percent(96%) were serous histological type. The ECOG performance score was 0 in 70% ofpatients and 1 in 28% of patients, overall. All patients had received first-line platinum-based therapy and bevacizumab. First-line treatment outcomes at screening indicatedthat patients had no evidence of disease with complete macroscopic resection at initialdebulking surgery (32%, both arms), no evidence of disease/ CR with completemacroscopic resection at interval debulking surgery (31%, both arms), no evidence ofdisease/ CR in patients who had either incomplete resection (at initial or intervaldebulking surgery) or no debulking surgery (15%, both arms) and patients with a partialresponse (22%, both arms). Thirty percent (30%) of patients in both arms had adeleterious mutation. Patients were not restricted by the surgical outcome with 65%having complete cytoreduction at initial or interval debulking surgery and 35% havingresidual macroscopic disease. Demographics and baseline disease characteristics werebalanced and comparable between the study and placebo arms in the Intention to Treat(ITT) population and also in the HRD-positive subgroup.Efficacy results from a biomarker subgroup analysis of 387 patients with HRD-positivetumors, identified post-randomization using the Myriad myChoice HRD Plus tumor test,who received Lynparza/bevacizumab (n=255) or placebo/bevacizumab (n=132), aresummarized in Table 19 and Figure 2. Results from a blinded independent review of PFSwere consistent. Overall survival data in this subpopulation were immature with 16%deaths.

Table 19 Efficacy Results - PAOLA-1 (HRD-positive status , InvestigatorAssessment)

*

†

Lynparza/bevacizumab(n=255)

Placebo/bevacizumab(n=132)

Progression-Free Survival Number of events (%) 87 (34%) 92 (70%) Median, months 37.2 17.7 Hazard ratio (95% CI) 0.33 (0.25, 0.45)CI Confidence interval

Figure 2 Kaplan-Meier Curves of Investigator-Assessed Progression-FreeSurvival – PAOLA-1 (HRD-positive status)

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*

Median follow-up of 27.4 months in Lynparza/bevacizumab arm and 27.5 months inplacebo/bevacizumab arm.The analysis was performed using an unstratified Cox proportional hazards model.

†

14.3 Maintenance Treatment of Recurrent Ovarian CancerThe efficacy of Lynparza was investigated in two randomized, placebo-controlled,double-blind, multi-center studies in patients with recurrent ovarian cancers who were inresponse to platinum-based therapy.SOLO-2The efficacy of Lynparza was evaluated in SOLO-2 (NCT01874353), a randomized (2:1)double-blind, placebo-controlled trial in patients with gBRCAm ovarian, fallopian tube, orprimary peritoneal cancer. Patients were randomized to Lynparza tablets 300 mg orallytwice daily or placebo until unacceptable toxicity or progressive disease. Randomizationwas stratified by response to last platinum chemotherapy (complete versus partial) andtime to disease progression in the penultimate platinum-based chemotherapy prior toenrollment (6-12 months versus >12 months). All patients had received at least twoprior platinum-containing regimens and were in response (complete or partial) to theirmost recent platinum-based regimen. The major efficacy outcome measure wasinvestigator-assessed PFS evaluated according to RECIST, version 1.1. An additionalefficacy outcome measure was OS.A total of 295 patients were randomized, 196 to Lynparza and 99 to placebo. Themedian age of patients treated with Lynparza was 56 years (range: 28 to 83) and 56

years (range: 39 to 78) among patients treated with placebo. The ECOG PS was 0 in83% of patients receiving Lynparza and 78% of patients receiving placebo. Of allpatients, 89% were White, 17% were enrolled in the U.S. or Canada, 47% were incomplete response to their most recent platinum-based regimen, and 40% had aprogression-free interval of 6-12 months since their penultimate platinum regimen. Priorbevacizumab therapy was reported for 17% of those treated with Lynparza and 20% ofthose receiving placebo. Approximately 44% of patients on the Lynparza arm and 37%on placebo had received three or more lines of platinum-based treatment.All patients had a deleterious or suspected deleterious germline BRCA mutation asdetected either by a local test (n=236) or central Myriad CLIA test (n=59), subsequentlyconfirmed by BRACAnalysis CDx (n=286).SOLO-2 demonstrated a statistically significant improvement in investigator-assessedPFS in patients randomized to Lynparza as compared with placebo. Results from ablinded independent review were consistent. The final analysis of OS did not reachstatistical significance. Efficacy results are presented in Table 20 and Figures 3 and 4.

Table 20 Efficacy Results - SOLO-2 (Investigator Assessment)Lynparza tablets

(n=196)Placebo(n=99)

*

†

Progression-Free Survival

107 (55%) 80 (81%)

Median, months 19.1 5.5 Hazard ratio (95% CI) 0.30 (0.22, 0.41) p-value <0.0001Overall SurvivalNumber of events (%) 116 (59) 65 (66) Median, months 51.7 38.8 Hazard ratio (95% CI) 0.74 (0.54, 1.00) p-value p=0.0537

Figure 3 Kaplan-Meier Curves of Investigator-Assessed Progression-FreeSurvival – SOLO-2

®

Hazard ratio from a Cox proportional hazards model including response to last platinumchemotherapy (complete response versus partial response) and time to disease progression inthe penultimate platinum-based chemotherapy prior to enrollment (6-12 month versus >12months) as covariates.The p-value is derived from a stratified log-rank test.

Number of events (%)

*†

*†

Figure 4 Kaplan-Meier Curves of Overall Survival – SOLO-2

Study 19The efficacy of Lynparza was evaluated in Study 19 (NCT00753545), a randomized (1:1)double-blind, placebo-controlled trial in patients with platinum-sensitive ovarian cancerwho had received 2 or more previous platinum-containing regimens. Patients wererandomized to Lynparza capsules 400 mg orally twice daily or placebo until unacceptabletoxicity or progressive disease. Randomization was stratified by response to lastplatinum chemotherapy (complete response versus partial response), time to diseaseprogression in the penultimate platinum-based chemotherapy (6-12 months versus >12months), and descent (Jewish versus non-Jewish). The major efficacy outcome measurewas investigator-assessed PFS according to RECIST, version 1.0.A total of 265 patients were randomized, 136 to Lynparza and 129 to placebo. Themedian age of patients treated with Lynparza was 58 years (range: 21 to 89) and 59years (range 33 to 84) among patients treated with placebo. ECOG PS was 0 in 81% ofpatients receiving Lynparza and 74% of patients receiving placebo. Of all patients, 97%were White, 19% were enrolled in the US or Canada, 45% were in complete responsefollowing their most recent platinum chemotherapy regimen, and 40% had aprogression-free interval of 6-12 months since their penultimate platinum. Priorbevacizumab therapy was reported for 13% of patients receiving Lynparza and 16% ofpatients receiving placebo.A retrospective analysis for germline BRCA mutation status, some performed using theMyriad test, indicated that 36% (n=96) of patients from the ITT population haddeleterious gBRCA mutation, including 39% (n=53) of patients on Lynparza and 33%(n=43) of patients on placebo.

Efficacy results are presented in Table 21 and Figure 5. Study 19 demonstrated astatistically significant improvement in investigator-assessed PFS in patients treated withLynparza versus placebo.

Table 21 Efficacy Results - Study 19 (Investigator Assessment)

*

†‡

Lynparza capsules(n=136)

Placebo(n=129)

Progression-Free Survival Number of events (%) 60 (44%) 94 (73%) Median, months 8.4 4.8 Hazard ratio (95% CI) 0.35 (0.25, 0.49) p-value <0.0001Overall Survival Number of events (%) 98 (72%) 112 (87%) Median, months 29.8 27.8 Hazard ratio (95% CI) 0.73 (0.55, 0.95)

Figure 5 Kaplan-Meier Curves of Investigator-Assessed Progression-FreeSurvival - Study 19

Hazard ratio from a Cox proportional hazards model including response to last platinumchemotherapy (complete response versus partial response), time to disease progression in thepenultimate platinum-based chemotherapy (6-12 months versus >12 months) and Jewishdescent (yes versus no) as covariates.The p-value is derived from a Cox proportional hazards model.Without adjusting for multiple analyses.

*†

‡

14.4 Advanced Germline BRCA-mutated Ovarian Cancer Treated with 3 orMore Prior Lines of ChemotherapyThe efficacy of Lynparza was investigated in a single-arm study of patients withdeleterious or suspected deleterious gBRCAm advanced cancers. A total of 137 patientswith measurable, advanced gBRCAm ovarian cancer treated with three or more priorlines of chemotherapy were enrolled. All patients received Lynparza capsules 400 mgorally twice daily until disease progression or intolerable toxicity. The efficacy outcomemeasures were objective response rate (ORR) and duration of response (DOR) asassessed by the investigator according to RECIST, version 1.0.The median age of the patients was 58 years, the majority were White (94%) and 93%had an ECOG PS of 0 or 1. Deleterious or suspected deleterious gBRCAm status wasverified retrospectively in 97% (59/61) of the patients for whom blood samples wereavailable by the BRACAnalysis CDx .Efficacy results are summarized in Table 22.

Table 22 Overall Response and Duration of Response in Patients with gBRCA-mutated Advanced Ovarian Cancer Who Received 3 or More Lines of

ChemotherapyLynparza Capsules

n=137Objective Response Rate (95% CI) 34% (26, 42) Complete response 2% Partial response 32%Median DOR in months (95% CI) 7.9 (5.6, 9.6)

14.5 Treatment of Germline BRCA-mutated HER2-negative Metastatic BreastCancerThe efficacy of Lynparza was evaluated in OlympiAD (NCT02000622), an open-labelrandomized (2:1) study in patients with gBRCAm HER2-negative metastatic breastcancer. Patients were required to have received treatment with an anthracycline (unlesscontraindicated) and a taxane, in the neoadjuvant, adjuvant or metastatic setting.Patients with hormone receptor-positive disease must have progressed on at least 1endocrine therapy (adjuvant or metastatic), or have disease that the treating healthcareprovider believed to be inappropriate for endocrine therapy. Patients with prior platinumtherapy were required to have no evidence of disease progress during platinumtreatment. No prior treatment with a PARP inhibitor was permitted. Patients wererandomized to Lynparza tablets 300 mg orally twice daily or healthcare provider’s choiceof chemotherapy (capecitabine, eribulin, or vinorelbine, at standard doses) untilprogression or unacceptable toxicity. Randomization was stratified by prior use ofchemotherapy for metastatic disease (yes vs no), hormone receptor status (hormonereceptor positive vs triple negative), and previous use of platinum-based chemotherapy(yes vs no). The major efficacy outcome measure was PFS assessed by blindedindependent central review (BICR) using RECIST version 1.1.A total of 302 patients were randomized, 205 to Lynparza and 97 to chemotherapy.Among the 205 patients treated with Lynparza, the median age was 44 years (range: 22

TM

to 76), 65% were White, 4% were males and all the patients had an ECOG PS of 0 or 1.Approximately 50% of patients had triple-negative tumors and 50% had estrogenreceptor and/or progesterone receptor positive tumors and the proportions werebalanced across treatment arms. Patients in each treatment arm had received a medianof 1 prior chemotherapy regimen for metastatic disease; approximately 30% had notreceived a prior chemotherapy regimen for metastatic breast cancer. Twenty-onepercent of patients in the Lynparza arm and 14% in the chemotherapy arm had receivedplatinum therapy for metastatic disease. Seven percent of patients in each treatmentarm had received platinum therapy for localized disease.Of the 302 patients randomized onto OlympiAD, 299 were tested with the BRACAnalysisCDx and 297 were confirmed to have deleterious or suspected deleterious gBRCAmstatus; 202 were randomized to the Lynparza arm and 95 to the healthcare provider’schoice of chemotherapy arm.A statistically significant improvement in PFS was demonstrated for the Lynparza armcompared to the chemotherapy arm. Efficacy data for OlympiAD are displayed in Table23 and Figure 6. Consistent results were observed across patient subgroups defined bystudy stratification factors. An exploratory analysis of investigator-assessed PFS wasconsistent with the BICR-assessed PFS results.

Table 23 Efficacy Results - OlympiAD (BICR-assessed)

*

†‡

Lynparza tablets(n=205)

Chemotherapy(n=97)

Progression-Free Survival Number of events (%) 163 (80%) 71 (73%) Median, months 7.0 4.2 Hazard ratio (95% CI) 0.58 (0.43, 0.80) p-value 0.0009Patients with MeasurableDisease

n=167 n=66

Objective Response Rate(95% CI)

52% (44, 60) 23% (13, 35)

Overall Survival Number of events (%) 130 (63%) 62 (64%) Median, months 19.3 17.1 Hazard ratio (95% CI) 0.90 (0.66, 1.23)

Figure 6 Kaplan-Meier Curves of Progression-Free Survival - OlympiAD

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Hazard ratio is derived from a stratified log-rank test, stratified by ER, PgR negative versus ER andor PgR positive and prior chemotherapy (yes versus no).For PFS, p-value (2-sided) was compared to 0.05.Response based on confirmed responses. The confirmed complete response rate was 7.8% forLynparza compared to 1.5% for chemotherapy arm.

*†

‡

*

14.6 First-Line Maintenance Treatment of Germline BRCA-mutatedMetastatic Pancreatic AdenocarcinomaThe efficacy of Lynparza was evaluated in POLO (NCT02184195), a randomized (3:2),double-blind placebo-controlled, multi-center trial. Patients were required to havemetastatic pancreatic adenocarcinoma with a deleterious or suspected deleteriousgermline BRCA mutation (gBRCAm) and absence of disease progression after receipt offirst-line platinum-based chemotherapy for at least 16 weeks. Patients were randomizedto receive Lynparza tablets 300 mg orally twice daily or placebo until disease progressionor unacceptable toxicity. The major efficacy outcome measure was PFS by BICR usingRECIST, version 1.1 modified to assess patients with clinical complete response at entrywho were assessed as having no evidence of disease unless they had progressed basedon the appearance of new lesions. Additional efficacy outcome measures were OS andORR.A total of 154 patients were randomized, 92 to Lynparza and 62 to placebo. The medianage was 57 years (range 36 to 84); 54% were male; 92% were White, 4% were Asian,and 3% were Black; baseline ECOG PS was 0 (67%) or 1 (31%). The median time frominitiation of first-line platinum-based chemotherapy to randomization was 5.8 months(range 3.4 to 33.4 months). Seventy-five percent (75%) of patients receivedFOLFIRINOX with a median of 9 cycles (range 4-61), 8% received FOLFOX or XELOX, 4%received GEMOX, and 3% received gemcitabine plus cisplatin; 49% achieved a completeor partial response to platinum-based chemotherapy.All patients had a deleterious or suspected deleterious germline BRCA-mutation as

® ®

detected by the Myriad BRACAnalysis or BRACAnalysis CDx at a central laboratoryonly (n=106), local BRCA test only (n=4), or both local and central testing (n=44).Among the 150 patients with central test results, 30% had a mutation in BRCA1; 69%had a mutation in BRCA2; and 1 patient (1%) had mutations in both BRCA1 and BRCA2.Efficacy results of POLO are provided in Table 24 and Figure 7.

Table 24 Efficacy Results - POLO (BICR-assessed)

*

†

Lynparza tablets(n=92)

Placebo(n=62)

Progression-Free Survival Number of events (%) 60 (65%) 44 (71%) Median, months (95% CI) 7.4 (4.1, 11.0) 3.8 (3.5, 4.9) Hazard ratio (95% CI) 0.53 (0.35, 0.81) p-value 0.0035Patients with MeasurableDisease

n=78 n=52

Objective Response Rate(95% CI)

23% (14, 34) 12% (4, 23)

Complete response (%) 2 (2.6) 0 Partial response (%) 16 (21) 6 (12)Duration of Response (DOR) Median time in months(95% CI)

25 (15, NC) 4 (2, NC)

NC Not calculable

The result of an OS interim analysis conducted based on 67% information fraction didnot show a statistically significant improvement in OS for Lynparza compared toplacebo.Figure 7 Kaplan-Meier Curves of BICR-Assessed Progression-Free Survival –POLO

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Number of events: Progression - Lynparza 55, placebo 44; death before BICR-documentedprogression - Lynparza 5, placebo 0Hazard ratio, 95% CI, and p-value calculated from a log-rank test. A hazard ratio <1 favorsLynparza.

*

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14.7 HRR Gene-mutated Metastatic Castration-Resistant Prostate CancerThe efficacy of Lynparza was evaluated in PROfound (NCT02987543), randomized,open-label, multi-center trial that evaluated the efficacy of Lynparza 300 mg twice dailyversus a comparator arm of investigator’s choice of enzalutamide or abirateroneacetate in men with metastatic castration-resistant prostate cancer (mCRPC). Allpatients received a GnRH analog or had prior bilateral orchiectomy. Patients needed tohave progressed on prior enzalutamide or abiraterone for the treatment of metastaticprostate cancer and/or CRPC and have a tumor mutation in one of 15 genes involved inthe homologous recombination repair (HRR) pathway.Patients were divided into two cohorts based on HRR gene mutation status. Patientswith mutations in either BRCA1, BRCA2, or ATM were randomized in Cohort A; patientswith mutations among 12 other genes involved in the HRR pathway (BARD1, BRIP1,CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, orRAD54L) were randomized in Cohort B; patients with co-mutations (BRCA1, BRCA2, orATM plus a Cohort B gene) were assigned to Cohort A. Although patients with PPP2R2Agene mutations were enrolled in the trial, Lynparza is not indicated for the treatment ofpatients with this gene mutation due to unfavorable risk-benefit. Patients wererandomized (2:1), 256 to Lynparza arm and 131 to enzalutamide or abiraterone acetatearm; in Cohort A there were 245 (162 Lynparza arm and 83 in enzalutamide orabiraterone acetate arm) and in Cohort B there were 142 patients (94 in Lynparza armand 48 in enzalutamide or abiraterone acetate arm). Randomization was stratified by

prior receipt of taxane chemotherapy and presence of measurable disease by RECIST1.1. Treatment was continued until objective radiological disease progression determinedby BICR. Upon radiological progression confirmed by BICR, patients randomized toenzalutamide or abiraterone acetate were given the option to switch to olaparib. Patientswith HRR gene mutations were identified by tissue-based testing using the FoundationMedicine FoundationOne clinical trial HRR assay performed at a central laboratory.Determination of deleterious or suspected deleterious somatic or germline HRR mutationstatus in line with the FDA approved mutation classification and testing criteria for theFoundation Medicine F1CDx tissue-based assay and assessment of the germline-BRCAstatus using the Myriad BRACAnalysis CDx blood-based assay was performedretrospectively. Representation of individual gene mutations by cohort is provided inTable 25. No patients were enrolled who had mutations in two of the 15 pre-specifiedHRR genes: FANCL and RAD51C.

Table 25 Frequency of Patients with HRR Mutations Enrolled in PROfound

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HRR Mutation Cohort AN=245n (%)

Cohort BN=142n (%)

Single mutation 224 (91) 135 (95) BRCA2 127 (52) 1 (<1) ATM 84 (34) 2 (1) BRCA1 13 (5) 0 CDK12 0 89 (63) CHEK2 0 12 (8) PPP2R2A 0 10 (7) RAD51B 0 5 (4) RAD54L 0 5 (4) PALB2 0 4 (3) BRIP1 0 3 (2) CHEK1 0 2 (1) BARD1 0 1 (<1) RAD51D 0 1 (<1)Co-occurring mutation 21 (9) 7 (5)

In Cohort A+B, the median age was 69 years (range: 47 to 91 years) in both arms; 69%were White, 29% were Asian, and 1% were Black. The ECOG performance score was 0or 1 in most patients (95%) in both arms. In patients treated with Lynparza, theproportion of patients with RECIST 1.1 measurable disease at baseline was 58%,including 17% with lung and 10% with liver metastases, respectively. At randomization,66% of patients had received prior taxane chemotherapy, 40% had receivedenzalutamide, 38% had received abiraterone acetate, and 20% had received bothenzalutamide and abiraterone acetate. Patient characteristics were well-balanced

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Three patients with single BRCA2 or ATM gene mutations and 1 patient with co-occurringBRCA2+CDK12 gene mutations were incorrectly assigned to Cohort B.Lynparza is not indicated for patients with PPP2R2A mutations.Patients with co-occurring mutations (BRCA1, BRCA2, or ATM plus a Cohort B gene) wereassigned to Cohort A.

*

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‡

between arms.The major efficacy outcome of the study was radiological progression free survival(rPFS) (Cohort A) as determined by BICR using RECIST version 1.1 and Prostate CancerClinical Trials Working Group 3 (PCWG3) (bone) criteria. Additional efficacy outcomesincluded confirmed objective response rate (ORR) (Cohort A), rPFS (combined CohortsA+B) as assessed by BICR, and overall survival (OS) (Cohort A).PROfound demonstrated a statistically significant improvement in BICR-assessed rPFSfor Lynparza compared to investigator’s choice of enzalutamide or abiraterone acetatein Cohort A and Cohort A+B. In an exploratory analysis for patients in Cohort B, themedian rPFS was 4.8 months for Lynparza vs 3.3 months for comparator with a HR of0.88 (95% CI 0.58, 1.36). The major efficacy outcome was supported by a statisticallysignificant improvement in ORR by BICR for patients with measurable disease at baselinein Cohort A. In Cohort B, ORR by BICR was 3.7% (95% CI 0.5, 12.7) in Lynparza treatedpatients and 8.3% (95% CI 1.0, 27.0) in patients treated with enzalutamide orabiraterone acetate.The final analysis of overall survival (OS) demonstrated a statistically significantimprovement in OS in patients randomized to Lynparza compared to patients in theenzalutamide or abiraterone acetate arm in Cohort A.Efficacy results of PROfound are provided in Tables 26 and 27 and Figures 8 and 9.

Table 26 Efficacy Results - PROfound (BICR-assessed)Cohort A Cohort A+B

Lynparzatablets(n=162)

Enzalutamideor

Abirateroneacetate(n=83)

Lynparzatablets(n=256)

Enzalutamideor

Abirateroneacetate(n=131)

Radiological Progression-Free Survival (rPFS) Number of events (%) 106 (65) 68 (82) 180 (70) 99 (76) Median (95% CI), in months 7.4 (6.2, 9.3) 3.6 (1.9, 3.7) 5.8 (5.5,

7.4) 3.5 (2.2, 3.7) Hazard ratio (95% CI) 0.34 (0.25, 0.47) 0.49 (0.38, 0.63) p-value <0.0001 <0.0001Confirmed ORRPatients with measurable diseaseat baseline

n=84 n=43 - -

ORR, n (%) 28 (33) 1 (2) - - (95% CI) (23, 45) (0, 12) - - p-value <0.0001 -Overall Survival n=162 n=83 - - Number of events (%) 91 (56) 57 (69) - - Median (95% CI), in months 19.1 (17.4,

23.4)14.7 (11.9,

18.8)- -

Hazard ratio (95% CI) 0.69 (0.50, 0.97) - p-value 0.0175 -

*

†‡

†‡

*

†

‡

CI Confidence interval

Figure 8 Kaplan-Meier Curves of BICR-Assessed Radiological Progression-Free Survival – PROfound – Cohort A

Consistent results were observed in exploratory analyses of rPFS for patients whoreceived or did not receive prior taxane therapy and for those with germline-BRCAmutations identified using the Myriad BRACAnalysis CDx assay compared with thosewith BRCA mutations identified using the Foundation Medicine F1CDx assay.Figure 9 Kaplan-Meier Curves of Overall Survival – PROfound – Cohort A

Although 10 patients with PPP2R2A mutation were included in all analyses of Cohort A+B,Lynparza is not indicated for this population due to unfavorable risk-benefit.The HR and CI were calculated using a Cox proportional hazards model adjusted for prior taxaneuse and measurable disease. An HR <1 favors Lynparza 300 mg bd.The analysis was performed using the log-rank test stratified by prior taxane use and measurabledisease.

Response data by HRR mutations for patients in the Lynparza arm are presented inTable 27. In the comparator arm of Cohorts A and B, a total of three patients achieved apartial response, including one patient with an ATM mutation alone and 2 patients withco-occurring mutations (one with PALB2+PPP2R2A and one with CDK12+PALB2).

Table 27 Response Rate and Duration of Response by HRR Mutation inPatients with Measurable Disease at Baseline on the Lynparza Arm –

PROfound (BICR-assessed)HRR mutation

Single mutationBRCA2

ATM

CDK12

*Patients(N=138)

Confirmed ORR†

n (%) 95% CI

43 24 (56) (40, 71)

30 3 (10) (2, 27)

CDK12

BRCA1

CHEK2

BRIP1

PALB2

CHEK1

RAD51B

RAD51D

RAD54L

Co-occurring mutationsBRCA2/CDK12

BRCA2/ATM

BRCA2/BARD1

BRCA2/CHEK2

CDK12/CHEK1

CDK12/PALB2

BRCA2/CDK12/CHEK2

BRCA2/CHEK2/RAD51D

34 2 (6) (1, 20)

6 SD, PD (4), NE NA

4 SD (2), PD (2) NA

2 SD, PD NA

2 SD, PD NA

1 PD NA

1 SD NA

1 PD NA

1 SD NA

2 PR, SD NA

2 SD, SD NA

1 PD NA

1 SD NA

1 SD NA

1 PD NA

1 PD NA

1 SD NA

PR Partial response; SD Stable disease; PD Progressive disease; NE Not evaluable;NA Not applicable due to small numbers or lack of response.

*

†

16 HOW SUPPLIED/STORAGE AND HANDLINGLynparza is available as 150 mg and 100 mg tablets.

•

•

Store at 20ºC to 25ºC (68ºF to 77ºF), excursions permitted to 15ºC to 30ºC (59ºF to86ºF) [see USP Controlled Room Temperature]. Store in original bottle to protect frommoisture.

17 PATIENT COUNSELING INFORMATIONAdvise the patient to read the FDA-approved patient labeling (Medication Guide).MDS/AMLAdvise patients to contact their healthcare provider if they experience weakness, feelingtired, fever, weight loss, frequent infections, bruising, bleeding easily, breathlessness,blood in urine or stool, and/or laboratory findings of low blood cell counts, or a need forblood transfusions. This may be a sign of hematological toxicity or a more seriousuncommon bone marrow problem called ‘myelodysplastic syndrome’ (MDS) or ‘acutemyeloid leukemia’ (AML) which have been reported in patients treated with Lynparza [seeWarnings and Precautions (5.1)].PneumonitisAdvise patients to contact their healthcare provider if they experience any new orworsening respiratory symptoms including shortness of breath, fever, cough, orwheezing [see Warnings and Precautions (5.2)].Embryo-Fetal ToxicityInform pregnant women of the risk to a fetus and potential loss of the pregnancy.Advise females to inform their healthcare provider of known or suspected pregnancy[see Use in Specific Populations (8.1)].

No patients with FANCL or RAD51C enrolled. Three patients with PPP2R2A mutations hadmeasurable disease, however, Lynparza is not indicated for patients with PPP2R2A mutation.In patients with a single BRCA2 mutation the median duration of response in the Lynparza arm(n=24) was 5.6 months (95% C.I: 5.5, 9.2). In the 3 responders with a single ATM mutation in theLynparza arm, the duration of response ranged from 5.8+ to 9.0 months. In the 2 responders witha single CDK12 mutation in the Lynparza arm, the duration of response was 3.7 and 7.2 months.+ denotes ongoing response.

NA Not applicable due to small numbers or lack of response.

150 mg tablets: green to green/grey, oval, bi-convex, film-coated tablet, withdebossment ‘OP150’ on one side and plain on the reverse, are available in:

∘∘

Bottles of 60 tablets (NDC 0310-0679-60) andBottles of 120 tablets (NDC 0310-0679-12).

100 mg tablets: yellow to dark yellow, oval, bi-convex, film-coated tablet, withdebossment ‘OP100’ on one side and plain on the reverse, are available in:

∘∘

Bottles of 60 tablets (NDC 0310-0668-60) andBottles of 120 tablets (NDC 0310-0668-12).

Advise females of reproductive potential to use effective contraception during treatmentwith Lynparza and for 6 months after the last dose [see Use in Specific Populations(8.3)].Advise male patients with female partners of reproductive potential or who are pregnantto use effective contraception during treatment and for 3 months after receiving the lastdose of Lynparza. Advise male patients not to donate sperm during therapy and for 3months following the last dose of Lynparza [see Warnings and Precautions (5.3) and Usein Specific Populations (8.3)].

Venous Thromboembolic EventsAdvise patients with metastatic castration-resistant prostate cancer to immediatelyreport any signs or symptoms of thromboembolism such as pain or swelling in anextremity, shortness of breath, chest pain, tachypnea, and tachycardia [see Warningsand Precautions (5.4)].LactationAdvise patients not to breastfeed while taking Lynparza and for one month afterreceiving the last dose [see Use in Specific Populations (8.2)].Drug InteractionsAdvise patients and caregivers to inform their healthcare provider of all concomitantmedications, including prescription medicines, over-the-counter drugs, vitamins, andherbal products. Inform patients to avoid grapefruit, grapefruit juice, Seville oranges,and Seville orange juice while taking Lynparza [see Drug Interactions (7.2)].Nausea/VomitingAdvise patients that mild or moderate nausea and/or vomiting is very common inpatients receiving Lynparza and that they should contact their healthcare provider whowill advise on available antiemetic treatment options [see Adverse Reactions (6.1)].Distributed by:AstraZeneca Pharmaceuticals LPWilmington, DE 19850© AstraZeneca 2021

Medication GuideLynparza (Lin-par-zah)

(olaparib)tablets

What is the most important information I should know about Lynparza?Lynparza may cause serious side effects, including:Bone marrow problems called Myelodysplastic Syndrome (MDS) or AcuteMyeloid Leukemia (AML). Some people who have ovarian cancer or breast cancerand who have received previous treatment with chemotherapy, radiotherapy or certainother medicines for their cancer have developed MDS or AML during treatment withLynparza. MDS or AML may lead to death. If you develop MDS or AML, your healthcare

®

provider will stop treatment with Lynparza.Symptoms of low blood cell counts are common during treatment with Lynparza, butcan be a sign of serious bone marrow problems, including MDS or AML. Symptoms mayinclude:

••••

••••

Your healthcare provider will do blood tests to check your blood cell counts:

•••

Lung problems (pneumonitis). Tell your healthcare provider if you have any new orworsening symptoms of lung problems, including shortness of breath, fever, cough, orwheezing. Your healthcare provider may do a chest x-ray if you have any of thesesymptoms. Your healthcare provider may temporarily or completely stop treatment ifyou develop pneumonitis. Pneumonitis may lead to death.Blood clots (Venous Thromboembolic Events). Some people with prostate cancerwho take Lynparza along with gonadotropin-releasing hormone (GnRH) analog therapymay develop a blood clot in a deep vein, usually in the leg (venous thrombosis) or a clotin the lung (pulmonary embolism). Tell your healthcare provider if you have anysymptoms such as pain or swelling in an extremity, shortness of breath, chest pain,breathing that is more rapid than normal (tachypnea), or heart beats faster than normal(tachycardia). Your healthcare provider will monitor you for these symptoms and mayprescribe blood thinner medicine.What is Lynparza?Lynparza is a prescription medicine used to treat adults who have:

•

•

•

•

weaknessweight lossfeverfrequent infections

blood in urine or stoolshortness of breathfeeling very tiredbruising or bleeding more easily

before treatment with Lynparzaevery month during treatment with Lynparzaweekly if you have low blood cell counts that last a long time. Your healthcareprovider may stop treatment with Lynparza until your blood cell counts improve.

advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer with acertain type of inherited (germline) or acquired (somatic) abnormal BRCA gene.Lynparza is used alone as maintenance treatment after the cancer has respondedto your first treatment with platinum-based chemotherapy. Your healthcareprovider will perform a test to make sure that Lynparza is right for you.advanced ovarian cancer, fallopian tube cancer or primary peritoneal cancer with acertain type of abnormal BRCA gene or a positive laboratory tumor test forgenomic instability called HRD. Lynparza is used in combination with another anti-cancer medicine, bevacizumab, as maintenance treatment after the cancer hasresponded to your first treatment with platinum-based chemotherapy. Yourhealthcare provider will perform a test to make sure that Lynparza is right for you.ovarian cancer, fallopian tube cancer, or primary peritoneal cancer, as maintenancetreatment, when the cancer has come back. Lynparza is used after the cancer hasresponded to treatment with platinum-based chemotherapy.advanced ovarian cancer with a certain type of abnormal inherited BRCA gene, andhave received treatment with 3 or more prior types of chemotherapy medicines.Your healthcare provider will perform a test to make sure that Lynparza is right foryou.

•

•

•

It is not known if Lynparza is safe and effective in children.Before taking Lynparza, tell your healthcare provider about all of yourmedical conditions, including if you:

•••

•

Tell your healthcare provider about all the medicines you take, includingprescription and over-the-counter medicines, vitamins, and herbal supplements. TakingLynparza and certain other medicines may affect how Lynparza works and may causeside effects.How should I take Lynparza?

you.a certain type of abnormal inherited BRCA gene, human epidermal growth factorreceptor 2 (HER2)-negative breast cancer that has spread to other parts of thebody (metastatic). You should have received chemotherapy medicines, eitherbefore or after your cancer has spread. If you have hormone receptor (HR)-positive disease, you should have been treated with hormonal therapy. Yourhealthcare provider will perform a test to make sure that Lynparza is right for you.metastatic pancreatic cancer with a certain type of abnormal inherited BRCA gene.Lynparza is used as maintenance treatment after your cancer has not progressedon at least 16 weeks of treatment with platinum-based chemotherapy. Yourhealthcare provider will perform a test to make sure that Lynparza is right for you.prostate cancer with certain inherited or acquired abnormal genes calledhomologous recombination repair (HRR genes). Lynparza is used when the cancerhas spread to other parts of the body (metastatic), and no longer responds to amedical or surgical treatment that lowers testosterone, and has progressed aftertreatment with enzalutamide or abiraterone. Your healthcare provider will perform atest to make sure Lynparza is right for you.

have lung or breathing problemshave kidney problemsare pregnant, become pregnant, or plan to become pregnant. Lynparza can harmyour unborn baby and may cause loss of pregnancy (miscarriage).

∘

∘

∘

∘

If you are able to become pregnant, your healthcare provider may do apregnancy test before you start treatment with Lynparza.Females who are able to become pregnant should use effective birth control(contraception) during treatment with Lynparza and for 6 months after thelast dose of Lynparza. Talk to your healthcare provider about birth controlmethods that may be right for you. Tell your healthcare provider right away ifyou become pregnant or think you might be pregnant following treatment withLynparza.Males with female partners who are pregnant or able to become pregnantshould use effective birth control (contraception) during treatment withLynparza and for 3 months after the last dose of Lynparza.Do not donate sperm during treatment with Lynparza and for 3 months afteryour final dose.

are breastfeeding or plan to breastfeed. It is not known if Lynparza passes intoyour breast milk. Do not breastfeed during treatment with Lynparza and for 1month after receiving the last dose of Lynparza. Talk to your healthcare providerabout the best way to feed your baby during this time.

How should I take Lynparza?

••

••

•••••

•

•

What should I avoid while taking Lynparza?Avoid grapefruit, grapefruit juice, Seville oranges and Seville orange juice duringtreatment with Lynparza since they may increase the level of Lynparza in your blood.What are the possible side effects of Lynparza?Lynparza may cause serious side effects.See “What is the most important information I should know aboutLynparza?”The most common side effects of Lynparza are:

•

••••••

••••••

These are not all of the possible side effects of Lynparza.Call your healthcare provider for medical advice about side effects. You may report sideeffects to FDA at 1-800-FDA-1088.How should I store Lynparza?

••

Keep Lynparza and all medicines out of reach of children.

Take Lynparza tablets exactly as your healthcare provider tells you.Do not change your dose or stop taking Lynparza unless your healthcare providertells you to. Your healthcare provider may temporarily stop treatment withLynparza or change your dose of Lynparza if you experience side effects.Your healthcare provider will decide how long you stay on treatment.Do not take more than 4 Lynparza tablets in 1 day. If you have any questionsabout Lynparza, please talk to your healthcare provider or pharmacist.Take Lynparza by mouth 2 times a day.Each dose should be taken about 12 hours apart.Swallow Lynparza tablets whole. Do not chew, crush, dissolve, or divide the tablets.Take Lynparza with or without food.If you are taking Lynparza for prostate cancer and you are receiving gonadotropin-releasing hormone (GnRH) analog therapy, you should continue with this treatmentduring your treatment with Lynparza unless you have had a surgery to lower theamount of testosterone in your body (surgical castration).If you miss a dose of Lynparza, take your next dose at your usual scheduled time.Do not take an extra dose to make up for a missed dose.If you take too much Lynparza, call your healthcare provider or go to the nearesthospital emergency room right away.

nausea or vomiting. Tell your healthcare provider if you get nausea or vomiting.Your healthcare provider may prescribe medicines to treat these symptoms.

tiredness or weaknesslow red blood cell countsdiarrhealoss of appetiteheadachechanges in the way food tastes

coughlow white blood cell countsshortness of breathdizzinessindigestion or heartburnlow platelet counts

Store Lynparza at room temperature, between 68°F to 77°F (20°C to 25°C).Store Lynparza in the original bottle to protect it from moisture.

General information about the safe and effective use of Lynparza.Medicines are sometimes prescribed for purposes other than those listed in aMedication Guide. Do not use Lynparza for a condition for which it was not prescribed.Do not give Lynparza to other people, even if they have the same symptoms you have.It may harm them.You can ask your healthcare provider or pharmacist for information about Lynparzathat is written for health professionals.What are the ingredients in Lynparza?Active ingredient: olaparibInactive ingredients:Tablet contains: copovidone, mannitol, colloidal silicon dioxide and sodium stearylfumarateTablet coating contains: hypromellose, polyethylene glycol 400, titanium dioxide, ferricoxide yellow and ferrosoferric oxide (150 mg tablet only)Lynparza is a registered trademark of the AstraZeneca group of companies.© AstraZeneca 2021Distributed by:AstraZeneca Pharmaceuticals LPWilmington, DE 19850For more information, call 1-800-236-9933 or go to www.Lynparza.com.

This Medication Guide has been approved by the U.S. Food and DrugAdministration. Revised: 3/2021

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL – 100 mgNDC 0310-0668-60Lynparza(olaparib) tablets100 mgDispense accompanyingMedication Guide to each patient.60 TabletsRx onlyAstraZeneca

®

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL – 150 mgNDC 0310-0679-12Lynparza(olaparib) tablets150 mgDispense accompanyingMedication Guide to each patient.120 TabletsRx onlyAstraZeneca

®

LYNPARZA olaparib tablet, film coated

Product InformationProduct Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0310-0668

Route of Administration ORAL

Active Ingredient/Active MoietyIngredient Name Basis of Strength Strength

OLAPARIB (UNII: WOH1JD9AR8) (OLAPARIB - UNII:WOH1JD9AR8) OLAPARIB 100 mg

Inactive IngredientsIngredient Name Strength

HYPROMELLOSE, UNSPECIFIED (UNII: 3NXW29V3WO) TITANIUM DIOXIDE (UNII: 15FIX9V2JP) POLYETHYLENE GLYCOL 400 (UNII: B697894SGQ) FERRIC OXIDE YELLOW (UNII: EX438O2MRT) WATER (UNII: 059QF0KO0R) FERROSOFERRIC OXIDE (UNII: XM0M87F357) COPOVIDONE K25-31 (UNII: D9C330MD8B) SILICON DIOXIDE (UNII: ETJ7Z6XBU4)

MANNITOL (UNII: 3OWL53L36A) SODIUM STEARYL FUMARATE (UNII: 7CV7WJK4UI)

Product CharacteristicsColor YELLOW (opaque) Score no scoreShape OVAL (biconvex) Size 14mmFlavor Imprint Code OP;100;plainContains

Packaging# Item Code Package Description Marketing Start

DateMarketing End

Date1 NDC:0310-0668-

6060 in 1 BOTTLE; Type 0: Not a CombinationProduct 08/17/2017

2 NDC:0310-0668-12

120 in 1 BOTTLE; Type 0: Not a CombinationProduct 08/17/2017

Marketing InformationMarketingCategory

Application Number or MonographCitation

Marketing StartDate

Marketing EndDate

NDA NDA208558 08/17/2017

LYNPARZA olaparib tablet, film coated

Product InformationProduct Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0310-0679

Route of Administration ORAL

Active Ingredient/Active MoietyIngredient Name Basis of Strength Strength

OLAPARIB (UNII: WOH1JD9AR8) (OLAPARIB - UNII:WOH1JD9AR8) OLAPARIB 150 mg

Inactive IngredientsIngredient Name Strength

HYPROMELLOSE, UNSPECIFIED (UNII: 3NXW29V3WO) TITANIUM DIOXIDE (UNII: 15FIX9V2JP) COPOVIDONE K25-31 (UNII: D9C330MD8B) SILICON DIOXIDE (UNII: ETJ7Z6XBU4) SODIUM STEARYL FUMARATE (UNII: 7CV7WJK4UI) FERRIC OXIDE YELLOW (UNII: EX438O2MRT) WATER (UNII: 059QF0KO0R)

AstraZeneca Pharmaceuticals LP

POLYETHYLENE GLYCOL 400 (UNII: B697894SGQ) MANNITOL (UNII: 3OWL53L36A) FERROSOFERRIC OXIDE (UNII: XM0M87F357)

Product CharacteristicsColor GREEN (grey) Score no scoreShape OVAL (bi-convex) Size 14mmFlavor Imprint Code OP150Contains

Packaging# Item Code Package Description Marketing Start

DateMarketing End

Date1 NDC:0310-0679-

6060 in 1 BOTTLE; Type 0: Not a CombinationProduct 08/17/2017

2 NDC:0310-0679-12

120 in 1 BOTTLE; Type 0: Not a CombinationProduct 08/17/2017

3 NDC:0310-0679-95

60 in 1 BOTTLE; Type 0: Not a CombinationProduct 08/31/2017

Marketing InformationMarketingCategory

Application Number or MonographCitation

Marketing StartDate

Marketing EndDate

NDA NDA208558 08/17/2017

Labeler - AstraZeneca Pharmaceuticals LP (054743190)

Registrant - AstraZeneca PLC (230790719)

Revised: 6/2021